BCL11B (CTIP2) is a nuclear C2H2 zinc-finger transcriptional regulator that controls target transcription through context-dependent activation, repression and chromatin-cofactor recruitment. It recognizes regulatory DNA and promotes IL2 expression in activated CD4+ T cells. In the human microglial HIV-1 promoter context, recruitment through Sp1 allows CTIP2 to assemble HDAC1/2 and SUV39H1-containing repressive machinery. BCL11B can also be stably incorporated into mammalian SWI/SNF complexes. In hematopoietic progenitors it supports T-lineage development and regulates chemokine-responsive migration. Human variants can alter DNA recognition and cause combined immune and neurodevelopmental abnormalities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: BCL11B recognizes cis-regulatory DNA as a transcription factor. Reason: Direct IL2 promoter recognition in PMID:16809611 corroborates the inherited cis-regulatory DNA-binding activity. Supporting Evidence: |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: The transferred cis-regulatory DNA-binding activity is independently supported in human cells. Reason: PMID:16809611 demonstrates BCL11B binding at the IL2 promoter. This corroborates the mouse ortholog transfer without claiming a new audit of its donor experiment. Supporting Evidence: |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: BCL11B can activate RNA polymerase II transcription in an appropriate cellular context. Reason: Activated CD4+ T-cell IL2 experiments support the activator activity. Retention does not imply that BCL11B activates every target or exclude its repressive roles. Supporting Evidence: |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding transcription-factor activity captures the context-dependent regulatory function. Reason: Direct IL2-site recognition and transcriptional activation support this broad DNA-binding transcription-factor activity. In the HIV-1 promoter setting, BCL11B instead recruits repressive chromatin partners through Sp1; that additional mechanism is not evidence for direct BCL11B DNA recognition at the viral promoter. The broad term accommodates target-dependent transcriptional regulation. |
| GO:0005515 protein binding | IPI PMID:17245431 Recruitment of chromatin-modifying enzymes by CTIP2 promotes... | MODIFY | Summary: The SUV39H1 interaction supports histone methyltransferase binding. Reason: PMID:17245431 reports SUV39H1 association and a mapped in-vitro pull-down. Refine the partner-binding function; SUV39H1 supplies the catalytic activity. Proposed replacements: histone methyltransferase binding Supporting Evidence: PMID:17245431 DNA-bound CTIP2 also associates with the histone methyltransferase SUV39H1 |
| GO:0005515 protein binding | IPI PMID:17245431 Recruitment of chromatin-modifying enzymes by CTIP2 promotes... | MODIFY | Summary: The HDAC1 interaction supports histone deacetylase binding. Reason: PMID:17245431 documents HDAC1-containing CTIP2 complexes and domain mapping. The specific enzyme-binding term is preferable to generic protein binding. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:17245431 CTIP2 recruits histone deacetylase (HDAC)1 and HDAC2 |
| GO:0005515 protein binding | IPI PMID:17245431 Recruitment of chromatin-modifying enzymes by CTIP2 promotes... | MODIFY | Summary: The HDAC2 interaction supports histone deacetylase binding. Reason: PMID:17245431 also demonstrates HDAC2 association. Refine this separate source row without assigning the partner enzyme activity to BCL11B. Proposed replacements: histone deacetylase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23752268 The functional interactome landscape of the human histone de... | MODIFY | Summary: The reported HDAC1 association supports a specific enzyme-binding annotation. Reason: The PMID:23752268 Discussion explicitly identifies BCL11B among HDAC1 interactions in the human CEM T-cell interactome. Histone deacetylase binding is more informative; this affinity-purification study does not establish a purified binary interaction. Proposed replacements: histone deacetylase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23752268 The functional interactome landscape of the human histone de... | MODIFY | Summary: The curated HDAC2 interaction can be refined to histone deacetylase binding. Reason: The source IPI assertion names HDAC2, and independent complex-association and recruitment experiments in PMID:17245431 substantiate BCL11B association with this enzyme. GO:0042826 captures the supported partner class without assigning deacetylase chemistry to BCL11B. The exact HDAC2 supplementary entry in the CEM T-cell interactome was not independently recovered. This functional refinement relies on the combined evidence; it does not claim that the source-specific supplementary record or a purified binary interaction was verified. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The curated HDAC1 interaction can be refined to histone deacetylase binding. Reason: The source IPI assertion names HDAC1, and independent complex-association and recruitment experiments in PMID:17245431 substantiate BCL11B association with this enzyme. GO:0042826 captures the supported partner class without assigning deacetylase chemistry to BCL11B. The individual BioPlex pair and its cell-line assignment were not independently inspected. This functional refinement relies on the combined evidence; it does not claim that the source-specific supplementary record or a purified binary interaction was verified. Proposed replacements: histone deacetylase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The curated HDAC2 interaction can be refined to histone deacetylase binding. Reason: The source IPI assertion names HDAC2, and independent complex-association and recruitment experiments in PMID:17245431 substantiate BCL11B association with this enzyme. GO:0042826 captures the supported partner class without assigning deacetylase chemistry to BCL11B. The individual BioPlex pair and its cell-line assignment were not independently inspected. This functional refinement relies on the combined evidence; it does not claim that the source-specific supplementary record or a purified binary interaction was verified. Proposed replacements: histone deacetylase binding |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear activity agrees with BCL11B transcriptional regulation. Reason: Nuclear promoter occupancy and the UniProt nuclear localization corroborate the IBA cellular location. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization is supported independently of the combined electronic mapping. Reason: Nuclear promoter occupancy and the UniProt localization support the combined electronic cellular-component assertion. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleoplasmic localization fits the chromatin-associated regulatory protein. Reason: Nuclear extracts, promoter occupancy and stable chromatin-regulatory complexes support a nucleoplasmic pool. This assessment corroborates the term, without claiming an independent reconstruction of the ARBA rule. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9934021 | ACCEPT | Summary: The Reactome nucleoplasm assertion agrees with independent nuclear evidence. Reason: R-HSA-9934021 describes mouse neural-progenitor BAF context rather than a new human localization assay. Human nuclear promoter and complex evidence supports the location while preserving that pathway-source limitation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9934024 | ACCEPT | Summary: Nucleoplasmic localization is consistent with the chromatin-complex context. Reason: R-HSA-9934024 places BCL11A/B in a BAF assembly context and leaves some subtype distributions unresolved. Independent human nuclear evidence supports nucleoplasm; no universal BAF-subtype assignment or autonomous ATPase activity is inferred. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: BCL11B directly regulates RNA polymerase II transcription. Reason: Promoter recognition and regulatory-cofactor association establish an active transcriptional role. The electronic process annotation agrees with this mechanism, beyond a developmental perturbation phenotype alone. |
| GO:0016514 SWI/SNF complex | IDA PMID:23644491 Proteomic and bioinformatic analysis of mammalian SWI/SNF co... | ACCEPT | Summary: BCL11B is a stable SWI/SNF-associated subunit in the studied context. Reason: PMID:23644491 includes human T-cell co-sedimentation, biochemical stability and reciprocal-immunoprecipitation evidence following mouse discovery experiments. Retain the IDA membership without extending exclusive complex occupancy to all cell types. Supporting Evidence: |
| GO:0016514 SWI/SNF complex | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic SWI/SNF membership is supported by direct human evidence. Reason: The independently supported human complex association in PMID:23644491 corroborates the combined mapping. BCL11B membership does not confer the catalytic remodeling ATPase activity of SMARCA subunits. Supporting Evidence: |
| GO:0035701 hematopoietic stem cell migration | IMP PMID:27959755 Multisystem Anomalies in Severe Combined Immunodeficiency wi... | KEEP AS NON CORE | Summary: BCL11B affects hematopoietic progenitor migration through transcriptional regulation. Reason: PMID:27959755 reports altered chemokine-receptor expression and increased migration after BCL11B knockdown in human CD34 progenitors, complemented by zebrafish positioning experiments. Retain the established developmental process as non-core; it is distinct from the protein’s defining molecular activity. Supporting Evidence: |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | UNDECIDED | Summary: Neuron-projection localization requires the underlying ortholog evidence. Reason: The mouse Q99PV8 transfer asserts a cellular location, not a role in making projections. Its supporting localization experiment was not recovered, and nuclear transcriptional function neither establishes nor excludes a smaller projection-localized pool. No confident removal is justified. Supporting Evidence: GO_REF:0000107 |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: The broad DNA-binding term can be refined to double-stranded sequence-specific binding. Reason: Regulatory DNA recognition is supported by direct IL2 promoter-binding experiments and the existing IDA double-stranded-DNA assertion. GO:1990837 is more specific; the original ortholog source fields remain unchanged. Proposed replacements: sequence-specific double-stranded DNA binding |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Positive transcriptional regulation is supported on BCL11B itself. Reason: Activated T-cell IL2 experiments directly support the inherited positive transcriptional-regulation activity. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:16809611 BCL11B participates in the activation of IL2 gene expression... | ACCEPT | Summary: BCL11B promotes IL2 transcription in activated CD4+ T cells. Reason: PMID:16809611 reports promoter occupancy, direct site binding and gain/loss perturbations of IL2 expression. These establish a transcriptional role in that activation context without implying every target is activated. Supporting Evidence: |
| GO:0097535 lymphoid lineage cell migration into thymus | IMP PMID:27959755 Multisystem Anomalies in Severe Combined Immunodeficiency wi... | KEEP AS NON CORE | Summary: BCL11B contributes to the regulation of thymic progenitor migration. Reason: PMID:27959755 combines human chemokine-response experiments with zebrafish thymic-seeding and partial-rescue evidence. Preserve this downstream developmental role as non-core rather than equating BCL11B with a chemokine receptor or motility effector. Supporting Evidence: |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Sequence-specific double-stranded DNA binding is independently established. Reason: The PMID:28473536 study-wide abstract describes human TF SELEX but the individual BCL11B motif/construct entry was not recovered. Direct IL2-site binding independently corroborates the curated IDA activity; no methylated-DNA preference is inferred. |
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Download this section (compressed HTML)Q: Which cell-specific experiments support the transferred neuron-projection location of BCL11B, and do they resolve the protein isoform?
Q: What are the precise assay and cell-line assignments of the original HDAC2 interactome entry and both BioPlex BCL11B–HDAC pairs? Their source provenance remains unresolved despite independent support for histone deacetylase binding.
Q: Which endogenous targets establish direct sequence-specific BCL11B DNA recognition coupled to repression, as distinct from Sp1-recruited corepression? PMID:17245431 supports the latter at the HIV-1 promoter, so it does not by itself justify a NEW GO:0001227 assertion. A separate GO:0003714 transcription corepressor activity proposal would require its own source, comparator and nonredundancy assessment.
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