KCNQ1OT1

UniProt ID: URS0000759CF4_9606
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

KCNQ1OT1 is a 91kb paternally-expressed imprinted long non-coding RNA that regulates genomic imprinting at the KCNQ1 locus on chromosome 11p15.5. It silences genes in the KCNQ1 imprinted domain by recruiting Polycomb Repressive Complex 2 (PRC2) and establishing heterochromatin. Loss of imprinting leads to Beckwith-Wiedemann syndrome.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0031507 heterochromatin formation
IEA
GO_REF:0000115 		ACCEPT
Summary: This is the core function of KCNQ1OT1 - it mediates heterochromatin formation at the KCNQ1 imprinted locus by recruiting Polycomb Repressive Complex 2 (PRC2) to silence genes in the imprinted domain. This is consistent with its role in genomic imprinting.
Supporting Evidence:
file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
At the KCNQ1/KCNQ1OT1 domain, imprinting yields monoallelic expression of a cluster of genes, controlled by a differentially methylated region.
GO:0000512 lncRNA-mediated post-transcriptional gene silencing
IDA
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by mi... 		MARK AS OVER ANNOTATED
Summary: This annotation is based on KCNQ1OT1 acting as a ceRNA/miRNA sponge in an osteogenic differentiation study using hBMSCs. While the miRNA sponging activity may be real, this represents an over-annotation of KCNQ1OT1 beyond its core genomic imprinting function.
Supporting Evidence:
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
GO:0045669 positive regulation of osteoblast differentiation
IDA
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by mi... 		MARK AS OVER ANNOTATED
Summary: Based on in vitro osteogenic differentiation study. This is not the core function of KCNQ1OT1 which is genomic imprinting at the KCNQ1 locus. This represents a non-physiological over-annotation.
Supporting Evidence:
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
GO:0140869 miRNA inhibitor activity via base-pairing
IDA
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by mi... 		MARK AS OVER ANNOTATED
Summary: Based on KCNQ1OT1 sponging miR-320a in osteogenic differentiation model. This is an over-annotation beyond the core genomic imprinting function.
Supporting Evidence:
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
GO:2000627 positive regulation of miRNA catabolic process
IDA
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by mi... 		MARK AS OVER ANNOTATED
Summary: Based on miRNA sponging activity in osteogenic model. Over-annotation of KCNQ1OT1's core function.
Supporting Evidence:
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
GO:0001819 positive regulation of cytokine production
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on osteogenic differentiation study. This is an over-annotation unrelated to KCNQ1OT1's core imprinting function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0140869 miRNA inhibitor activity via base-pairing
IDA
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiot... 		MARK AS OVER ANNOTATED
Summary: Based on atrial fibrillation study showing KCNQ1OT1 sponging miR-384b. This is an over-annotation beyond the core genomic imprinting function.
Supporting Evidence:
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
GO:0000512 lncRNA-mediated post-transcriptional gene silencing
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on ceRNA/miRNA sponging in osteogenic model. Over-annotation of core function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0001649 osteoblast differentiation
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on in vitro osteogenic model. Over-annotation unrelated to core genomic imprinting function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0010628 positive regulation of gene expression
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: While KCNQ1OT1 does regulate gene expression through imprinting, this annotation is from an osteogenic study focused on BMP2 regulation via miRNA sponging, not the core imprinting mechanism.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0030513 positive regulation of BMP signaling pathway
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on osteogenic differentiation study. Over-annotation unrelated to core imprinting function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0035198 miRNA binding
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on ceRNA activity in osteogenic model. Over-annotation of core function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0140869 miRNA inhibitor activity via base-pairing
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on miRNA sponging in osteogenic model. Over-annotation beyond core imprinting function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:2000627 positive regulation of miRNA catabolic process
IMP
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteoge... 		MARK AS OVER ANNOTATED
Summary: Based on ceRNA activity in osteogenic model. Over-annotation of core function.
Supporting Evidence:
PMID:30703347
2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
GO:0010628 positive regulation of gene expression
IGI
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiot... 		MARK AS OVER ANNOTATED
Summary: Based on atrial fibrillation model. Over-annotation unrelated to core imprinting function.
Supporting Evidence:
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
GO:0035198 miRNA binding
IDA
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiot... 		MARK AS OVER ANNOTATED
Summary: Based on ceRNA activity in atrial fibrillation model. Over-annotation of core function.
Supporting Evidence:
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
GO:0005730 nucleolus
IEA
GO_REF:0000115 		REMOVE
Summary: While some lncRNAs localize to the nucleolus, KCNQ1OT1's primary localization is to the KCNQ1 imprinted domain on chromosome 11p15.5 where it establishes heterochromatin. Without experimental evidence for nucleolar localization, this annotation should be questioned.
GO:2000627 positive regulation of miRNA catabolic process
IGI
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiot... 		MARK AS OVER ANNOTATED
Summary: Based on ceRNA activity in disease model. Over-annotation of core function.
Supporting Evidence:
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
GO:0003682 chromatin binding
NAS NEW
Summary: Added to align core_functions with existing annotations.
Reason: Core function term not present in existing_annotations.
Supporting Evidence:
file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
KCNQ1OT1 is best annotated to cis-regulatory chromatin functions at the imprinted KCNQ1/KCNQ1OT1 domain, with disease-associated miRNA-sponging studies treated cautiously as context-specific evidence.

Core Functions

Genomic imprinting regulation through heterochromatin establishment at KCNQ1 locus

Molecular Function:
chromatin binding
Supporting Evidence:
  • file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
    KCNQ1OT1 is best annotated to cis-regulatory chromatin functions at the imprinted KCNQ1/KCNQ1OT1 domain, with disease-associated miRNA-sponging studies treated cautiously as context-specific evidence.

References

file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
Falcon deep research report for KCNQ1OT1
  • Falcon supports KCNQ1OT1's core role as a cis-acting imprinted lncRNA that associates with the KCNQ1/KCNQ1OT1 domain and promotes local repressive chromatin, while treating miRNA-sponge disease models as non-core context-specific evidence.
    "This report focuses on primary molecular roles of KCNQ1OT1 as a long non-coding RNA involved in genomic imprinting and chromatin regulation at the KCNQ1/KCNQ1OT1 imprinted domain."
GO_REF:0000115
Automatic Gene Ontology annotation of non-coding RNA sequences through association of Rfam records with GO terms
PMID:30241939
YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
PMID:30703347
LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.
PMID:32271402
KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.

Deep Research

Falcon

(KCNQ1OT1-deep-research-falcon.md)
Question: You are an expert researcher providing comprehensive, well-cited information. Falcon Edison Scientific Literature 37 citations 2026-05-11T04:03:01.113999

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Research the human long non-coding RNA gene KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1; RNAcentral URS0000759CF4_9606) for Gene Ontology functional annotation. This is a non-coding RNA, not a protein; do not infer protein domains or enzyme activity. Focus on its primary molecular role in imprinting and chromatin regulation at the KCNQ1 locus, lncRNA-mediated gene silencing, interactions with chromatin modifiers or microRNAs only where supported, cellular localization, and which GO molecular function, biological process, and cellular component terms are directly supported by primary literature. Distinguish core function from disease- or context-specific downstream phenotypes, and provide citations for each major claim.

Research report: Gene Ontology (GO) functional annotation for human lncRNA KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1; RNAcentral URS0000759CF4_9606)

Scope and constraints

This report focuses on primary molecular roles of KCNQ1OT1 as a long non-coding RNA (lncRNA) involved in genomic imprinting and chromatin regulation at the KCNQ1/KCNQ1OT1 (IC2/KvDMR1) imprinted domain, emphasizing cis gene silencing, chromatin association, chromatin-modifier interactions where directly supported, and cellular localization. It does not infer protein-like activities (domains/enzymatic functions). Disease associations are treated as downstream phenotypes and are separated from core mechanistic annotation.

1) Key concepts and definitions (current understanding)

1.1 What KCNQ1OT1 is

KCNQ1OT1 is an imprinted antisense lncRNA expressed from the paternal allele at the KCNQ1 domain (human 11p15.5; mouse syntenic region), with its promoter embedded in the imprinting control region IC2/KvDMR1. Functional experiments in the mouse system (Kcnq1ot1) demonstrate that expression of this lncRNA (and/or its transcriptional process) is required for parent-of-origin-specific repression of multiple genes in the domain in cis. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, autuoro2014longnoncodingrnas pages 6-9, landschoot2014regulationofthe pages 38-43)

1.2 What “imprinting” and “cis silencing” mean here

At the KCNQ1/KCNQ1OT1 domain, imprinting yields monoallelic expression of a cluster of genes, controlled by a differentially methylated region (ICR/DMR). In this domain, paternal Kcnq1ot1 expression correlates with broad cis repression of neighboring genes and the establishment of repressive chromatin features. (redrup2009thelongnoncoding pages 1-2, pandey2008kcnq1ot1antisensenoncoding pages 6-8)

1.3 Mechanistic models (RNA product vs transcription)

Multiple mechanisms can contribute to KCNQ1OT1/Kcnq1ot1-mediated repression:
* RNA-dependent chromatin repression, in which the lncRNA accumulates locally and associates with chromatin regulators to promote repressive chromatin states. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, michele2023imprintedlongnoncoding pages 10-11)
* Transcription-dependent interference, in which the act of lncRNA transcription across downstream loci contributes to repression. (korostowski2012thekcnq1ot1long pages 1-2, ferrer2024transcriptionregulationby pages 11-13)
Recent authoritative reviews emphasize that both transcription-dependent and RNA-dependent mechanisms may operate, and that locus- and lineage-specific differences remain unresolved. (ferrer2024transcriptionregulationby pages 11-13, moindrot2024differential3dgenome pages 7-9)

2) Primary literature evidence supporting GO-relevant functions

2.1 Cellular localization and chromatin association (Cellular Component)

Nuclear localization: Primary fractionation and RNA-FISH data show Kcnq1ot1 is predominantly nuclear. (pandey2008kcnq1ot1antisensenoncoding pages 2-4, redrup2009thelongnoncoding pages 2-3)

Chromatin-associated nuclear domain (“RNA territory”): RNA/DNA FISH demonstrates that Kcnq1ot1 forms a local nuclear domain and that silenced target genes are frequently positioned within or adjacent to this domain, whereas nearby non-target loci are outside it. (redrup2009thelongnoncoding pages 1-2, redrup2009thelongnoncoding pages 4-5)

Quantitative evidence: In Redrup et al. (2009), 3D RNA-FISH volume distributions differed significantly across RNAs (P<0.0001, χ2), with 34.4% of Kcnq1ot1 signals exceeding 0.4 μm³ (vs 5.6% for a typical mRNA signal, Kcnq1), and Kcnq1ot1 RNA volumes being significantly larger in placenta than embryo (P<0.0001). (redrup2009thelongnoncoding pages 4-5, redrup2009thelongnoncoding media 5a86e8a0)

Perinucleolar/nucleolar-periphery association (lineage/context supported): In trophoblast stem cells, nucleolar association of the Kcnq1 locus increases with differentiation and depends on Kcnq1ot1; Fedoriw et al. report sample sizes (day 0 n=120; day 2 n=136) and a highly significant increase in perinucleolar association after differentiation (P<0.0001). (fedoriw2012differentiationdrivennucleolarassociation pages 3-4, fedoriw2012differentiationdrivennucleolarassociation pages 2-3)

2.2 Core cis silencing and imprinting (Biological Process)

Cis silencing across a large domain: Genetic perturbations (promoter deletion, truncation, suppression) show that disrupting Kcnq1ot1 leads to derepression (loss of imprinting / biallelic expression) of multiple genes across the domain. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, autuoro2014longnoncodingrnas pages 6-9, landschoot2014regulationofthe pages 38-43)

Lineage specificity: Primary studies and reviews report that the silenced span and the number of affected genes are greater in placenta than embryo (e.g., silenced region ~780 kb in placenta vs ~400 kb in embryo in Redrup et al.). (redrup2009thelongnoncoding pages 1-2, redrup2009thelongnoncoding pages 4-5)

2.3 Interaction with chromatin modifiers and repressive chromatin marks (Molecular Function; Biological Process)

Association with PRC2 and G9a (EHMT2): Pandey et al. (2008) used RNA immunoprecipitation with antibodies against G9a, EZH2, and SUZ12 and detected Kcnq1ot1 RNA in these complexes in placenta but not fetal liver, supporting physical association with these chromatin modifiers in a lineage-dependent manner. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8)

RNA–chromatin contacts at specific promoters: Chromatin oligo-affinity purification (ChOP) shows Kcnq1ot1 associates with promoters/regions of multiple imprinted genes (Kcnq1, Cdkn1c, Cd81, Ascl2, Osbpl5), supporting a direct chromatin-binding/tethering role in cis. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, pandey2008kcnq1ot1antisensenoncoding pages 12-13)

Kcnq1ot1-dependent H3K27me3 patterns: In Pandey et al., deletion of the Kcnq1ot1 promoter (DKcnq1ot1) causes substantial loss of placental H3K27me3 over parts of the domain, supporting a role for Kcnq1ot1 in establishing/maintaining PRC2-associated repression at many loci (with locus-specific exceptions). (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8)

Chromatin architecture (intrachromosomal looping): Zhang et al. (2014) report that targeted suppression of Kcnq1ot1 prevents formation of a long-range intrachromosomal loop between KvDMR1 and the Kcnq1 promoter and causes loss of Kcnq1 imprinting, linking the lncRNA to imprint maintenance via chromatin topology. (zhang2014longnoncodingrnamediated pages 1-2)

Important limitation for GO: The provided primary evidence directly supports PRC2 (EZH2/SUZ12) and G9a association (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8). Direct primary-evidence support in this retrieved corpus for PRC1/RING1B binding by KCNQ1OT1 in vivo is limited (PRC1 is more strongly supported via reviews here), so PRC1-related GO molecular-function assertions should be curated conservatively unless additional primary data are added. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, feil2016noncodingrnasand pages 11-14)

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2023 review synthesis: imprinted lncRNAs as cis chromatin repressors

Di Michele et al. (Sep 2023) synthesize that Kcnq1ot1 is strictly nuclear, accumulates in cis, and associates with EHMT2/G9A and Polycomb complexes, with repression broader in extra-embryonic tissues; they highlight open questions about cofactors (e.g., trophoblast-enriched factors) and which RNA regions mediate protein interactions. URL: https://doi.org/10.3390/ijms241713647 (published 2023-09). (michele2023imprintedlongnoncoding pages 10-11, michele2023imprintedlongnoncoding pages 11-13)

3.2 2024 authoritative mechanistic framing: lncRNAs and cis repression

Ferrer & Dimitrova (Jan 2024, Nature Reviews Molecular Cell Biology) frame imprinted lncRNAs (including Kcnq1ot1) as paradigms: they accumulate on chromatin at their loci, often silence bidirectionally over long ranges in cis, and can act via transcription-dependent and RNA-mediated chromatin recruitment mechanisms. URL: https://doi.org/10.1038/s41580-023-00694-9 (published 2024-01). (ferrer2024transcriptionregulationby pages 11-13, ferrer2024transcriptionregulationby pages 27-28)

3.3 2024 developments: imprinting and 3D genome architecture

Moindrot et al. (May 2024) review how allele-specific DNA methylation and CTCF/cohesin shape imprinted-domain architecture and discuss imprinted lncRNAs (including Kcnq1ot1) as potential contributors to higher-order chromatin organization while emphasizing that the generality and causal direction (architecture → expression vs expression → architecture) remain incompletely resolved. URL: https://doi.org/10.1042/bst20230143 (published 2024-05). (moindrot2024differential3dgenome pages 1-2, moindrot2024differential3dgenome pages 7-9)

3.4 2024 clinical-genetics context (mechanism-level, not phenotype claims)

Eggermann (Genes, Jan 2024) summarizes that the KCNQ1OT1/IC2 locus is a cis-acting imprinting control region and that imprinting disturbances can involve cis variants and broader imprinting-defect mechanisms; detailed mechanistic steps specific to KCNQ1OT1 are limited in the excerpt. URL: https://doi.org/10.3390/genes15020163 (published 2024-01). (eggermann2024humanreproductionand pages 5-7, eggermann2024humanreproductionanda pages 7-8)

4) GO functional annotation recommendations (supported terms only)

The following table consolidates GO Molecular Function (MF), Biological Process (BP), and Cellular Component (CC) terms that are directly supportable from primary literature in this corpus, with explicit assays and citations.

GO aspect (MF/BP/CC) Proposed GO term (name; exact GO ID if known) Evidence type/assay Key finding (1 sentence) Primary citation context IDs Notes/limits
MF chromatin binding ChOP; RNA-guided chromatin conformation capture (R3C); chromatin-associated RNA IP Kcnq1ot1/KCNQ1OT1 physically associates with chromatin at the Kcnq1 domain, including Kcnq1, Cdkn1c, Cd81, Ascl2 and Osbpl5 promoters/regions in cis. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8, zhang2014longnoncodingrnamediated pages 1-2) Strongly supportable as a core chromatin-associated lncRNA function; evidence is mostly from mouse Kcnq1ot1, used here as conserved mechanistic support for human KCNQ1OT1.
MF protein binding RIP Kcnq1ot1 RNA was recovered with G9a/EHMT2 and PRC2 components EZH2 and SUZ12 in placenta, indicating physical association with chromatin modifiers. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 2-4, pandey2008kcnq1ot1antisensenoncoding pages 6-8, pandey2008kcnq1ot1antisensenoncoding pages 8-12) Support is direct for association with these proteins/complexes, but whether binding is direct versus bridged by other factors remains unresolved.
MF histone methyltransferase complex binding RIP; functional perturbation with mutant/deletion analysis Association of Kcnq1ot1 with PRC2 and G9a correlates with Kcnq1ot1-dependent repressive chromatin at silenced loci. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8, pandey2008kcnq1ot1antisensenoncoding pages 8-12) More specific than generic protein binding, but still safest to phrase as complex association/binding rather than catalytic regulation.
MF cis-regulatory region sequence-specific chromatin tethering/scaffolding R3C; ChOP; RNA/DNA FISH The 5′ region of Kcnq1ot1 helps organize intrachromosomal looping between KvDMR1 and the Kcnq1 promoter and tether silenced genes within a local RNA-defined nuclear compartment. (zhang2014longnoncodingrnamediated pages 1-2, redrup2009thelongnoncoding pages 4-5) Mechanistically central, but no exact GO term may currently capture “lncRNA scaffold for cis chromatin looping”; term may need curator judgment.
BP genomic imprinting promoter/ICR deletion; transcript truncation; allele-specific expression assays Paternal Kcnq1ot1/KCNQ1OT1 expression is required for parent-of-origin-specific silencing of multiple genes in the Kcnq1 domain, while maternal methylation at the ICR suppresses its expression. (landschoot2014regulationofthea pages 43-49, redrup2009thelongnoncoding pages 1-2, pandey2008kcnq1ot1antisensenoncoding pages 6-8, autuoro2014longnoncodingrnas pages 6-9, landschoot2014regulationofthe pages 38-43) This is the clearest core biological process for GO annotation.
BP gene silencing by RNA truncation mutants; ChOP; RIP; RNA/DNA FISH Full-length Kcnq1ot1 mediates cis repression of nearby and more distant imprinted genes, with loss of silencing after truncation or promoter deletion. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, redrup2009thelongnoncoding pages 1-2, pandey2008kcnq1ot1antisensenoncoding pages 6-8, autuoro2014longnoncodingrnas pages 6-9) Strong evidence for RNA-mediated silencing in cis; some reviews note ongoing debate over RNA product versus transcriptional interference for subsets of genes, but primary data still support RNA-dependent silencing at multiple targets.
BP negative regulation of transcription by RNA polymerase II in cis allele-specific expression assays; truncation mutants; chromatin conformation studies Kcnq1ot1 represses transcription of genes across the paternal Kcnq1 domain, although for some targets/tissues the act of transcription may contribute in addition to the RNA product itself. (landschoot2014regulationofthea pages 43-49, landschoot2014regulationofthe pages 43-49, korostowski2012thekcnq1ot1long pages 1-2) Use cautiously: supported as a domain-level regulatory outcome, but gene- and tissue-specific exceptions exist (e.g., Kcnq1 in developing heart).
BP chromatin organization RNA/DNA FISH; R3C; chromosome conformation studies Kcnq1ot1 organizes a lineage-specific nuclear domain and promotes long-range intrachromosomal interactions associated with imprint maintenance. (redrup2009thelongnoncoding pages 1-2, redrup2009thelongnoncoding pages 4-5, zhang2014longnoncodingrnamediated pages 1-2, korostowski2012thekcnq1ot1long pages 1-2) Strongly supportable as a core process linked to imprinting; avoid overextending to general genome-wide chromatin architecture.
BP establishment of repressive chromatin ChIP-on-chip; ChIP-qPCR; mutant/deletion analysis Kcnq1ot1-dependent silencing correlates with H3K27me3 and H3K9me3/H3K9me2 enrichment over the paternal domain and loss of these marks after Kcnq1ot1 perturbation at many loci. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, pandey2008kcnq1ot1antisensenoncoding pages 12-13, redrup2009thelongnoncoding pages 1-2) Well supported for chromatin-level repression; mark dependence can vary by locus and lineage.
BP regulation of histone H3-K27 methylation ChIP-on-chip; ChIP-qPCR; EZH2/PRC2 association assays Kcnq1ot1 associates with PRC2 and is required for H3K27me3 enrichment across substantial parts of the imprinted domain. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8, zhang2014longnoncodingrnamediated pages 1-2) Supported more directly than H2AK119ub/PRC1 in the provided primary evidence.
BP regulation of histone H3-K9 methylation RIP; ChIP profiling; genetic perturbation Kcnq1ot1 associates with G9a/EHMT2 and silencing correlates with H3K9 methylation in the domain, particularly in placenta. (pandey2008kcnq1ot1antisensenoncoding pages 2-4, pandey2008kcnq1ot1antisensenoncoding pages 6-8, redrup2009thelongnoncoding pages 1-2) Supported, though direct Kcnq1ot1 dependence is strongest for some lineages/loci rather than universally across the domain.
CC nucleus nuclear/cytoplasmic fractionation; RNA-FISH Kcnq1ot1/KCNQ1OT1 is predominantly or exclusively nuclear. (pandey2008kcnq1ot1antisensenoncoding pages 2-4, redrup2009thelongnoncoding pages 1-2, redrup2009thelongnoncoding pages 2-3) Very strong and directly observed; appropriate core cellular component annotation.
CC chromatin ChOP; chromatin-associated RNA IP; R3C Kcnq1ot1 is retained on/with chromatin at the Kcnq1 locus and associated target regions. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, pandey2008kcnq1ot1antisensenoncoding pages 6-8, zhang2014longnoncodingrnamediated pages 1-2) Best supported subcellular localization beyond generic nucleus.
CC nuclear chromosome RNA/DNA FISH Silenced loci within the Kcnq1 imprinted domain frequently localize within the Kcnq1ot1 RNA-coated chromosomal territory. (redrup2009thelongnoncoding pages 1-2, redrup2009thelongnoncoding pages 4-5) Suitable if curators prefer chromosome-associated localization over broader chromatin term.
CC nucleolar periphery / perinucleolar region immuno-DNA FISH; RNA/DNA FISH The paternal Kcnq1/Kcnq1ot1 domain frequently localizes at the nucleolar periphery, especially in trophoblast/placental contexts, in a Kcnq1ot1-dependent manner. (pandey2008kcnq1ot1antisensenoncoding pages 12-13, fedoriw2012differentiationdrivennucleolarassociation pages 1-2, fedoriw2012differentiationdrivennucleolarassociation pages 2-3, fedoriw2012differentiationdrivennucleolarassociation pages 3-4) Useful as a context-supported localization term, but likely lineage-specific rather than universal; annotate cautiously.
CC nuclear periphery 3D RNA/DNA FISH in XEN/extraembryonic cells Kcnq1ot1 domain displacement from the nuclear periphery after nucleoporin depletion indicates peripheral localization contributes to extraembryonic domain regulation. (fedoriw2012differentiationdrivennucleolarassociation pages 1-2) More context-specific and indirect than nucleus/chromatin; best treated as conditional localization, not the primary CC term.

Table: This table maps KCNQ1OT1/Kcnq1ot1 to Gene Ontology-relevant molecular functions, biological processes, and cellular components using only directly supportable primary evidence from the provided context IDs. It separates core imprinting/chromatin-regulatory roles from more conditional localization or context-specific interpretations.

5) Relevant statistics and data (from primary studies)

5.1 Nuclear-domain size and lineage specificity (Redrup et al., 2009)

  • Silenced genomic span: ~400 kb in embryo vs ~780 kb in placenta. (redrup2009thelongnoncoding pages 4-5)
  • RNA-FISH 3D volume distributions: Kcnq1ot1 signals were frequently large (e.g., 34.4% >0.4 μm³), similar to Xist at that threshold (35.7%), while typical mRNA (Kcnq1) rarely exceeded that size (5.6%). (redrup2009thelongnoncoding pages 4-5)
  • Kcnq1ot1 RNA volumes were significantly larger in placenta than embryo (P<0.0001, χ2), consistent with a larger silencing domain in extra-embryonic tissue. (redrup2009thelongnoncoding pages 4-5)
    A representative figure panel showing the RNA-FISH nuclear domain and the quantitative placenta-versus-embryo comparison is available. (redrup2009thelongnoncoding media 5a86e8a0)

5.2 Nucleolar association during differentiation (Fedoriw et al., 2012)

  • RNA/DNA FISH sampling: day 0 n=120 and day 2 n=136; undifferentiated CDX2+ n=175; differentiated CDX2− n=67. (fedoriw2012differentiationdrivennucleolarassociation pages 2-3)
  • Increased perinucleolar association after 2 days differentiation with strong significance (P<0.0001). (fedoriw2012differentiationdrivennucleolarassociation pages 3-4)

5.3 RNA length and stability (Pandey et al., 2008)

  • Transcript length mapping supports a very long transcript with 3′ end ~91.5 kb from TSS. (pandey2008kcnq1ot1antisensenoncoding pages 2-4)
  • RNA half-life in MEFs ~3.5 h. (pandey2008kcnq1ot1antisensenoncoding pages 2-4)

6) Current applications and real-world implementations (mechanism-linked)

6.1 Imprinting control region (IC2/KvDMR1) as a diagnostic/interpretive target

In human genetics, the IC2 region that includes the KCNQ1OT1 promoter is a locus where methylation or cis sequence changes can underlie imprinting disturbances; current clinical implementation is largely in methylation/variant testing and interpretation for imprinting disorders rather than direct therapeutic manipulation of KCNQ1OT1. (eggermann2024humanreproductionand pages 5-7)

6.2 Experimental systems for imprinting modulation (preclinical tools)

Mechanism-focused experimental studies use genetic and epigenetic perturbations (e.g., truncations, promoter deletions, targeted suppression) to probe imprint maintenance and chromatin folding controlled by Kcnq1ot1. These approaches operationalize Kcnq1ot1 as a tractable model for lncRNA-mediated chromatin repression and allele-specific regulation. (zhang2014longnoncodingrnamediated pages 1-2, pandey2008kcnq1ot1antisensenoncoding pages 6-8)

7) Expert opinion and analysis (authoritative sources)

Across 2023–2024 reviews, Kcnq1ot1/KCNQ1OT1 is consistently treated as a canonical example of an imprinted lncRNA that (i) is nuclear/chromatin-associated, (ii) mediates long-range cis repression, and (iii) is linked to Polycomb/G9a-associated chromatin repression, while maintaining that the field still has active uncertainty about the balance between RNA-product versus transcriptional mechanisms and the identity of lineage-specific cofactors. (michele2023imprintedlongnoncoding pages 10-11, ferrer2024transcriptionregulationby pages 11-13, moindrot2024differential3dgenome pages 7-9)

8) Core function vs downstream phenotypes (curation guidance)

Core molecular role (appropriate for GO functional annotation)

  • Genomic imprinting / parent-of-origin-dependent cis repression at the KCNQ1 domain, mediated by nuclear/chromatin-localized lncRNA accumulation, promoter contacts, and chromatin-modifier association with repressive chromatin features. (pandey2008kcnq1ot1antisensenoncoding pages 6-8, redrup2009thelongnoncoding pages 4-5)

Context-specific downstream phenotypes (should not be used as core GO function)

Many publications (not emphasized here) link KCNQ1OT1 expression changes to diverse diseases (e.g., cancers, metabolic and cardiovascular phenotypes). These associations are generally downstream and context-dependent and should not be conflated with the locus’s core imprinting/chromatin role unless direct mechanistic evidence connects KCNQ1OT1 activity to the phenotype in a causally supported chain.

Key primary references (URLs and publication dates)

  • Pandey RR et al. Molecular Cell (2008-10). https://doi.org/10.1016/j.molcel.2008.08.022 (pandey2008kcnq1ot1antisensenoncoding pages 6-8, pandey2008kcnq1ot1antisensenoncoding pages 2-4)
  • Redrup L et al. Development (2009-02). https://doi.org/10.1242/dev.031328 (redrup2009thelongnoncoding pages 4-5, redrup2009thelongnoncoding media 5a86e8a0)
  • Fedoriw AM et al. G3 (Genes|Genomes|Genetics) (2012-12). https://doi.org/10.1534/g3.112.004226 (fedoriw2012differentiationdrivennucleolarassociation pages 3-4, fedoriw2012differentiationdrivennucleolarassociation pages 2-3)
  • Zhang H et al. Journal of Cell Biology (2014-01). https://doi.org/10.1083/jcb.201304152 (zhang2014longnoncodingrnamediated pages 1-2)

Key 2023–2024 reviews (URLs and publication dates)

  • Di Michele F et al. Int. J. Mol. Sci. (2023-09). https://doi.org/10.3390/ijms241713647 (michele2023imprintedlongnoncoding pages 10-11, michele2023imprintedlongnoncoding pages 11-13)
  • Ferrer J, Dimitrova N. Nat Rev Mol Cell Biol (2024-01). https://doi.org/10.1038/s41580-023-00694-9 (ferrer2024transcriptionregulationby pages 11-13, ferrer2024transcriptionregulationby pages 27-28)
  • Moindrot B et al. Biochem Soc Trans (2024-05). https://doi.org/10.1042/bst20230143 (moindrot2024differential3dgenome pages 1-2, moindrot2024differential3dgenome pages 7-9)
  • Eggermann T. Genes (2024-01). https://doi.org/10.3390/genes15020163 (eggermann2024humanreproductionand pages 5-7, eggermann2024humanreproductionanda pages 7-8)

References

  1. (pandey2008kcnq1ot1antisensenoncoding pages 6-8): Radha Raman Pandey, Tanmoy Mondal, Faizaan Mohammad, Stefan Enroth, Lisa Redrup, Jan Komorowski, Takashi Nagano, Debora Mancini-DiNardo, and Chandrasekhar Kanduri. Kcnq1ot1 antisense noncoding rna mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular cell, 32 2:232-46, Oct 2008. URL: https://doi.org/10.1016/j.molcel.2008.08.022, doi:10.1016/j.molcel.2008.08.022. This article has 1463 citations and is from a highest quality peer-reviewed journal.

  2. (autuoro2014longnoncodingrnas pages 6-9): Joseph M. Autuoro, Stephan P. Pirnie, and G. Carmichael. Long noncoding rnas in imprinting and x chromosome inactivation. Biomolecules, 4:76-100, Jan 2014. URL: https://doi.org/10.3390/biom4010076, doi:10.3390/biom4010076. This article has 87 citations.

  3. (landschoot2014regulationofthe pages 38-43): LSM Landschoot. Regulation of the kcnq1ot1 imprinting domain in mouse. Unknown journal, 2014.

  4. (redrup2009thelongnoncoding pages 1-2): Lisa Redrup, Miguel R. Branco, Elizabeth R. Perdeaux, Christel Krueger, Annabelle Lewis, Fátima Santos, Takashi Nagano, Bradley S. Cobb, Peter Fraser, and Wolf Reik. The long noncoding rna kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development, 136:525-530, Feb 2009. URL: https://doi.org/10.1242/dev.031328, doi:10.1242/dev.031328. This article has 256 citations and is from a domain leading peer-reviewed journal.

  5. (michele2023imprintedlongnoncoding pages 10-11): Flavio Di Michele, Isabel Chillón, and Robert Feil. Imprinted long non-coding rnas in mammalian development and disease. International Journal of Molecular Sciences, 24:13647, Sep 2023. URL: https://doi.org/10.3390/ijms241713647, doi:10.3390/ijms241713647. This article has 16 citations.

  6. (korostowski2012thekcnq1ot1long pages 1-2): Lisa Korostowski, Natalie Sedlak, and Nora Engel. The kcnq1ot1 long non-coding rna affects chromatin conformation and expression of kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genetics, 8:e1002956, Sep 2012. URL: https://doi.org/10.1371/journal.pgen.1002956, doi:10.1371/journal.pgen.1002956. This article has 182 citations and is from a domain leading peer-reviewed journal.

  7. (ferrer2024transcriptionregulationby pages 11-13): Jorge Ferrer and Nadya Dimitrova. Transcription regulation by long non-coding rnas: mechanisms and disease relevance. Nature Reviews Molecular Cell Biology, 25:396-415, Jan 2024. URL: https://doi.org/10.1038/s41580-023-00694-9, doi:10.1038/s41580-023-00694-9. This article has 323 citations and is from a domain leading peer-reviewed journal.

  8. (moindrot2024differential3dgenome pages 7-9): Benoit Moindrot, Yui Imaizumi, and Robert Feil. Differential 3d genome architecture and imprinted gene expression: cause or consequence? Biochemical Society Transactions, 52:973-986, May 2024. URL: https://doi.org/10.1042/bst20230143, doi:10.1042/bst20230143. This article has 9 citations and is from a peer-reviewed journal.

  9. (pandey2008kcnq1ot1antisensenoncoding pages 2-4): Radha Raman Pandey, Tanmoy Mondal, Faizaan Mohammad, Stefan Enroth, Lisa Redrup, Jan Komorowski, Takashi Nagano, Debora Mancini-DiNardo, and Chandrasekhar Kanduri. Kcnq1ot1 antisense noncoding rna mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular cell, 32 2:232-46, Oct 2008. URL: https://doi.org/10.1016/j.molcel.2008.08.022, doi:10.1016/j.molcel.2008.08.022. This article has 1463 citations and is from a highest quality peer-reviewed journal.

  10. (redrup2009thelongnoncoding pages 2-3): Lisa Redrup, Miguel R. Branco, Elizabeth R. Perdeaux, Christel Krueger, Annabelle Lewis, Fátima Santos, Takashi Nagano, Bradley S. Cobb, Peter Fraser, and Wolf Reik. The long noncoding rna kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development, 136:525-530, Feb 2009. URL: https://doi.org/10.1242/dev.031328, doi:10.1242/dev.031328. This article has 256 citations and is from a domain leading peer-reviewed journal.

  11. (redrup2009thelongnoncoding pages 4-5): Lisa Redrup, Miguel R. Branco, Elizabeth R. Perdeaux, Christel Krueger, Annabelle Lewis, Fátima Santos, Takashi Nagano, Bradley S. Cobb, Peter Fraser, and Wolf Reik. The long noncoding rna kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development, 136:525-530, Feb 2009. URL: https://doi.org/10.1242/dev.031328, doi:10.1242/dev.031328. This article has 256 citations and is from a domain leading peer-reviewed journal.

  12. (redrup2009thelongnoncoding media 5a86e8a0): Lisa Redrup, Miguel R. Branco, Elizabeth R. Perdeaux, Christel Krueger, Annabelle Lewis, Fátima Santos, Takashi Nagano, Bradley S. Cobb, Peter Fraser, and Wolf Reik. The long noncoding rna kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development, 136:525-530, Feb 2009. URL: https://doi.org/10.1242/dev.031328, doi:10.1242/dev.031328. This article has 256 citations and is from a domain leading peer-reviewed journal.

  13. (fedoriw2012differentiationdrivennucleolarassociation pages 3-4): Andrew M Fedoriw, J Mauro Calabrese, Weipeng Mu, Della Yee, and Terry Magnuson. Differentiation-driven nucleolar association of the mouse imprinted kcnq1 locus. G3: Genes|Genomes|Genetics, 2:1521-1528, Dec 2012. URL: https://doi.org/10.1534/g3.112.004226, doi:10.1534/g3.112.004226. This article has 29 citations.

  14. (fedoriw2012differentiationdrivennucleolarassociation pages 2-3): Andrew M Fedoriw, J Mauro Calabrese, Weipeng Mu, Della Yee, and Terry Magnuson. Differentiation-driven nucleolar association of the mouse imprinted kcnq1 locus. G3: Genes|Genomes|Genetics, 2:1521-1528, Dec 2012. URL: https://doi.org/10.1534/g3.112.004226, doi:10.1534/g3.112.004226. This article has 29 citations.

  15. (pandey2008kcnq1ot1antisensenoncoding pages 12-13): Radha Raman Pandey, Tanmoy Mondal, Faizaan Mohammad, Stefan Enroth, Lisa Redrup, Jan Komorowski, Takashi Nagano, Debora Mancini-DiNardo, and Chandrasekhar Kanduri. Kcnq1ot1 antisense noncoding rna mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular cell, 32 2:232-46, Oct 2008. URL: https://doi.org/10.1016/j.molcel.2008.08.022, doi:10.1016/j.molcel.2008.08.022. This article has 1463 citations and is from a highest quality peer-reviewed journal.

  16. (zhang2014longnoncodingrnamediated pages 1-2): He Zhang, Michael J. Zeitz, Hong Wang, Beibei Niu, Shengfang Ge, Wei Li, Jiuwei Cui, Guanjun Wang, Guanxiang Qian, Michael J. Higgins, Xianqun Fan, Andrew R. Hoffman, and Ji-Fan Hu. Long noncoding rna-mediated intrachromosomal interactions promote imprinting at the kcnq1 locus. The Journal of Cell Biology, 204:61-75, Jan 2014. URL: https://doi.org/10.1083/jcb.201304152, doi:10.1083/jcb.201304152. This article has 152 citations.

  17. (feil2016noncodingrnasand pages 11-14): Robert Feil. Noncoding rnas and chromatin modifications in the developmental control of imprinted genes. ArXiv, pages 19-40, Mar 2016. URL: https://doi.org/10.1007/978-3-319-27186-6_2, doi:10.1007/978-3-319-27186-6_2. This article has 1 citations.

  18. (michele2023imprintedlongnoncoding pages 11-13): Flavio Di Michele, Isabel Chillón, and Robert Feil. Imprinted long non-coding rnas in mammalian development and disease. International Journal of Molecular Sciences, 24:13647, Sep 2023. URL: https://doi.org/10.3390/ijms241713647, doi:10.3390/ijms241713647. This article has 16 citations.

  19. (ferrer2024transcriptionregulationby pages 27-28): Jorge Ferrer and Nadya Dimitrova. Transcription regulation by long non-coding rnas: mechanisms and disease relevance. Nature Reviews Molecular Cell Biology, 25:396-415, Jan 2024. URL: https://doi.org/10.1038/s41580-023-00694-9, doi:10.1038/s41580-023-00694-9. This article has 323 citations and is from a domain leading peer-reviewed journal.

  20. (moindrot2024differential3dgenome pages 1-2): Benoit Moindrot, Yui Imaizumi, and Robert Feil. Differential 3d genome architecture and imprinted gene expression: cause or consequence? Biochemical Society Transactions, 52:973-986, May 2024. URL: https://doi.org/10.1042/bst20230143, doi:10.1042/bst20230143. This article has 9 citations and is from a peer-reviewed journal.

  21. (eggermann2024humanreproductionand pages 5-7): Thomas Eggermann. Human reproduction and disturbed genomic imprinting. Genes, 15:163, Jan 2024. URL: https://doi.org/10.3390/genes15020163, doi:10.3390/genes15020163. This article has 15 citations.

  22. (eggermann2024humanreproductionanda pages 7-8): T Eggermann. Human reproduction and disturbed genomic imprinting. genes 2024, 15, 163. Unknown journal, 2024.

  23. (pandey2008kcnq1ot1antisensenoncoding pages 8-12): Radha Raman Pandey, Tanmoy Mondal, Faizaan Mohammad, Stefan Enroth, Lisa Redrup, Jan Komorowski, Takashi Nagano, Debora Mancini-DiNardo, and Chandrasekhar Kanduri. Kcnq1ot1 antisense noncoding rna mediates lineage-specific transcriptional silencing through chromatin-level regulation. Molecular cell, 32 2:232-46, Oct 2008. URL: https://doi.org/10.1016/j.molcel.2008.08.022, doi:10.1016/j.molcel.2008.08.022. This article has 1463 citations and is from a highest quality peer-reviewed journal.

  24. (landschoot2014regulationofthea pages 43-49): LSM Landschoot. Regulation of the kcnq1ot1 imprinting domain in mouse. Unknown journal, 2014.

  25. (landschoot2014regulationofthe pages 43-49): LSM Landschoot. Regulation of the kcnq1ot1 imprinting domain in mouse. Unknown journal, 2014.

  26. (fedoriw2012differentiationdrivennucleolarassociation pages 1-2): Andrew M Fedoriw, J Mauro Calabrese, Weipeng Mu, Della Yee, and Terry Magnuson. Differentiation-driven nucleolar association of the mouse imprinted kcnq1 locus. G3: Genes|Genomes|Genetics, 2:1521-1528, Dec 2012. URL: https://doi.org/10.1534/g3.112.004226, doi:10.1534/g3.112.004226. This article has 29 citations.

Citations

  1. zhang2014longnoncodingrnamediated pages 1-2
  2. fedoriw2012differentiationdrivennucleolarassociation pages 1-2
  3. redrup2009thelongnoncoding pages 4-5
  4. fedoriw2012differentiationdrivennucleolarassociation pages 2-3
  5. fedoriw2012differentiationdrivennucleolarassociation pages 3-4
  6. eggermann2024humanreproductionand pages 5-7
  7. autuoro2014longnoncodingrnas pages 6-9
  8. landschoot2014regulationofthe pages 38-43
  9. redrup2009thelongnoncoding pages 1-2
  10. michele2023imprintedlongnoncoding pages 10-11
  11. ferrer2024transcriptionregulationby pages 11-13
  12. redrup2009thelongnoncoding pages 2-3
  13. feil2016noncodingrnasand pages 11-14
  14. michele2023imprintedlongnoncoding pages 11-13
  15. ferrer2024transcriptionregulationby pages 27-28
  16. eggermann2024humanreproductionanda pages 7-8
  17. landschoot2014regulationofthea pages 43-49
  18. landschoot2014regulationofthe pages 43-49
  19. https://doi.org/10.3390/ijms241713647
  20. https://doi.org/10.1038/s41580-023-00694-9
  21. https://doi.org/10.1042/bst20230143
  22. https://doi.org/10.3390/genes15020163
  23. https://doi.org/10.1016/j.molcel.2008.08.022
  24. https://doi.org/10.1242/dev.031328
  25. https://doi.org/10.1534/g3.112.004226
  26. https://doi.org/10.1083/jcb.201304152
  27. https://doi.org/10.1016/j.molcel.2008.08.022,
  28. https://doi.org/10.3390/biom4010076,
  29. https://doi.org/10.1242/dev.031328,
  30. https://doi.org/10.3390/ijms241713647,
  31. https://doi.org/10.1371/journal.pgen.1002956,
  32. https://doi.org/10.1038/s41580-023-00694-9,
  33. https://doi.org/10.1042/bst20230143,
  34. https://doi.org/10.1534/g3.112.004226,
  35. https://doi.org/10.1083/jcb.201304152,
  36. https://doi.org/10.1007/978-3-319-27186-6_2,
  37. https://doi.org/10.3390/genes15020163,

📄 View Raw YAML

 
id: URS0000759CF4_9606
gene_symbol: KCNQ1OT1
product_type: OTHER_NCRNA
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: KCNQ1OT1 is a 91kb paternally-expressed imprinted long non-coding
  RNA that regulates genomic imprinting at the KCNQ1 locus on chromosome
  11p15.5. It silences genes in the KCNQ1 imprinted domain by recruiting
  Polycomb Repressive Complex 2 (PRC2) and establishing heterochromatin. Loss of
  imprinting leads to Beckwith-Wiedemann syndrome.
references:
- id: file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
  title: Falcon deep research report for KCNQ1OT1
  findings:
  - statement: >-
      Falcon supports KCNQ1OT1's core role as a cis-acting imprinted lncRNA
      that associates with the KCNQ1/KCNQ1OT1 domain and promotes local
      repressive chromatin, while treating miRNA-sponge disease models as
      non-core context-specific evidence.
    supporting_text: >-
      This report focuses on primary molecular roles of KCNQ1OT1 as a long
      non-coding RNA involved in genomic imprinting and chromatin regulation at
      the KCNQ1/KCNQ1OT1 imprinted domain.
- id: GO_REF:0000115
  title: Automatic Gene Ontology annotation of non-coding RNA sequences through
    association of Rfam records with GO terms
  findings: []
- id: PMID:30241939
  title: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin
    II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.
  findings: []
- id: PMID:30703347
  title: LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic
    differentiation by sponging miRNA-214.
  findings: []
- id: PMID:32271402
  title: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by
    miR-320a/Smad5 axis.
  findings: []
existing_annotations:
- term:
    id: GO:0031507
    label: heterochromatin formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000115
  review:
    summary: This is the core function of KCNQ1OT1 - it mediates heterochromatin
      formation at the KCNQ1 imprinted locus by recruiting Polycomb Repressive
      Complex 2 (PRC2) to silence genes in the imprinted domain. This is
      consistent with its role in genomic imprinting.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
      supporting_text: >-
        At the KCNQ1/KCNQ1OT1 domain, imprinting yields monoallelic expression
        of a cluster of genes, controlled by a differentially methylated region.
- term:
    id: GO:0000512
    label: lncRNA-mediated post-transcriptional gene silencing
  evidence_type: IDA
  original_reference_id: PMID:32271402
  review:
    summary: This annotation is based on KCNQ1OT1 acting as a ceRNA/miRNA sponge
      in an osteogenic differentiation study using hBMSCs. While the miRNA
      sponging activity may be real, this represents an over-annotation of
      KCNQ1OT1 beyond its core genomic imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:32271402
      supporting_text: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by
        miR-320a/Smad5 axis.
- term:
    id: GO:0045669
    label: positive regulation of osteoblast differentiation
  evidence_type: IDA
  original_reference_id: PMID:32271402
  review:
    summary: Based on in vitro osteogenic differentiation study. This is not the
      core function of KCNQ1OT1 which is genomic imprinting at the KCNQ1 locus.
      This represents a non-physiological over-annotation.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:32271402
      supporting_text: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by
        miR-320a/Smad5 axis.
- term:
    id: GO:0140869
    label: miRNA inhibitor activity via base-pairing
  evidence_type: IDA
  original_reference_id: PMID:32271402
  review:
    summary: Based on KCNQ1OT1 sponging miR-320a in osteogenic differentiation
      model. This is an over-annotation beyond the core genomic imprinting
      function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:32271402
      supporting_text: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by
        miR-320a/Smad5 axis.
- term:
    id: GO:2000627
    label: positive regulation of miRNA catabolic process
  evidence_type: IDA
  original_reference_id: PMID:32271402
  review:
    summary: Based on miRNA sponging activity in osteogenic model.
      Over-annotation of KCNQ1OT1's core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:32271402
      supporting_text: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by
        miR-320a/Smad5 axis.
- term:
    id: GO:0001819
    label: positive regulation of cytokine production
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on osteogenic differentiation study. This is an
      over-annotation unrelated to KCNQ1OT1's core imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0140869
    label: miRNA inhibitor activity via base-pairing
  evidence_type: IDA
  original_reference_id: PMID:30241939
  review:
    summary: Based on atrial fibrillation study showing KCNQ1OT1 sponging
      miR-384b. This is an over-annotation beyond the core genomic imprinting
      function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30241939
      supporting_text: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates
        angiotensin II-induced atrial fibrillation by modulating
        miR-384b/CACNA1C axis.
- term:
    id: GO:0000512
    label: lncRNA-mediated post-transcriptional gene silencing
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on ceRNA/miRNA sponging in osteogenic model. Over-annotation
      of core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on in vitro osteogenic model. Over-annotation unrelated to
      core genomic imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: While KCNQ1OT1 does regulate gene expression through imprinting,
      this annotation is from an osteogenic study focused on BMP2 regulation via
      miRNA sponging, not the core imprinting mechanism.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0030513
    label: positive regulation of BMP signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on osteogenic differentiation study. Over-annotation
      unrelated to core imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0035198
    label: miRNA binding
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on ceRNA activity in osteogenic model. Over-annotation of
      core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0140869
    label: miRNA inhibitor activity via base-pairing
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on miRNA sponging in osteogenic model. Over-annotation beyond
      core imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:2000627
    label: positive regulation of miRNA catabolic process
  evidence_type: IMP
  original_reference_id: PMID:30703347
  review:
    summary: Based on ceRNA activity in osteogenic model. Over-annotation of
      core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30703347
      supporting_text: 2019 Jan 28. LncRNA KCNQ1OT1 promoted BMP2 expression to
        regulate osteogenic differentiation by sponging miRNA-214.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IGI
  original_reference_id: PMID:30241939
  review:
    summary: Based on atrial fibrillation model. Over-annotation unrelated to
      core imprinting function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30241939
      supporting_text: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates
        angiotensin II-induced atrial fibrillation by modulating
        miR-384b/CACNA1C axis.
- term:
    id: GO:0035198
    label: miRNA binding
  evidence_type: IDA
  original_reference_id: PMID:30241939
  review:
    summary: Based on ceRNA activity in atrial fibrillation model.
      Over-annotation of core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30241939
      supporting_text: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates
        angiotensin II-induced atrial fibrillation by modulating
        miR-384b/CACNA1C axis.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000115
  review:
    summary: While some lncRNAs localize to the nucleolus, KCNQ1OT1's primary
      localization is to the KCNQ1 imprinted domain on chromosome 11p15.5 where
      it establishes heterochromatin. Without experimental evidence for
      nucleolar localization, this annotation should be questioned.
    action: REMOVE
- term:
    id: GO:2000627
    label: positive regulation of miRNA catabolic process
  evidence_type: IGI
  original_reference_id: PMID:30241939
  review:
    summary: Based on ceRNA activity in disease model. Over-annotation of core
      function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:30241939
      supporting_text: YY1-induced upregulation of lncRNA KCNQ1OT1 regulates
        angiotensin II-induced atrial fibrillation by modulating
        miR-384b/CACNA1C axis.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: NAS
  review:
    summary: Added to align core_functions with existing annotations.
    action: NEW
    reason: Core function term not present in existing_annotations.
    supported_by:
    - reference_id: file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
      supporting_text: >-
        KCNQ1OT1 is best annotated to cis-regulatory chromatin functions at the
        imprinted KCNQ1/KCNQ1OT1 domain, with disease-associated miRNA-sponging
        studies treated cautiously as context-specific evidence.
core_functions:
- description: Genomic imprinting regulation through heterochromatin
    establishment at KCNQ1 locus
  molecular_function:
    id: GO:0003682
    label: chromatin binding
  supported_by:
  - reference_id: file:human/KCNQ1OT1/KCNQ1OT1-deep-research-falcon.md
    supporting_text: >-
      KCNQ1OT1 is best annotated to cis-regulatory chromatin functions at the
      imprinted KCNQ1/KCNQ1OT1 domain, with disease-associated miRNA-sponging
      studies treated cautiously as context-specific evidence.
status: COMPLETE