FOXG1

Summary: FOXG1 associates with chromatin at regulatory regions.

Reason: Endogenous FOXG1 ChIP and sequential FOXG1/TLE1 ChIP at regulatory regions in human BT048 cells support the TFClass chromatin-location assertion (PMID:24356439). The 300–500 bp cross-linked fragments establish regional chromatin association and co-occupancy; they leave direct base contacts and the fraction of FOXG1 bound to chromatin unresolved.

Summary: FOXG1 is a DNA-binding regulator of RNA polymerase II transcription.

Reason: The TFClass Pol II transcription-factor assertion is supported by complementary human experiments: target-specific HT-SELEX demonstrates motif recognition, GAL4-tethered human BF-1 represses a Pol II reporter, and endogenous FOXG1 occupies regulatory regions with TLE1 in BT048 cells. Each assay contributes a distinct part of the gene-level inference: GAL4 supplies the reporter tether, and ChIP measures regional occupancy. Purified native FOXG1–promoter affinity was not measured by these cellular assays.

Summary: Broad DNA binding is covered by FOXG1 sequence-specific double-stranded DNA binding.

Reason: Retain the original TAS reference while applying the same gene-level granularity judgment to both GO:0003677 rows. Independently verified target-specific HT-SELEX supports the existing GO:1990837 annotations, an is_a descendant through GO:0043565. Selected original Methods in PMID:7957066 describe FREAC2/3/4/7 constructs; the exact FOXG1-specific support for this historical TAS row was not recovered. This source limitation does not establish a wrong-gene citation or contradict FOXG1 DNA binding.

Summary: The historical DNA-binding assertion is less specific than the established double-stranded DNA-binding activity.

Reason: GO:1990837 is an is_a descendant of GO:0003677 and is independently supported for FOXG1. PMID:7959731 has an authentic abstract describing human clones and developmental expression, but its exact DNA-binding assay was not recovered. Its historical HFK1/HFK2/HFK3 interpretation must not create present-day alternative products; current UniProt documents likely sequencing errors. The original TAS identifier remains unchanged, and this specificity judgment does not certify unseen Methods.

Summary: The generic DNA-binding transcription-factor term is covered by the retained Pol II-specific activity.

Reason: The InterPro inference is biologically sound, but GO:0000981 is an is_a child of this unrestricted term and is already present. Human reporter and endogenous promoter-occupancy evidence support the more informative Pol II-specific gene-level activity. The family-derived source assertion is preserved; it is not treated as erroneous because a more specific annotation is available.

Summary: FOXG1 interacts with the transcriptional corepressor PLU-1/KDM5B.

Reason: Human BF-1 binds PLU-1/KDM5B in yeast two-hybrid and reciprocal tagged co-immunoprecipitation experiments (PMID:12657635). BF-1 VP-motif mutations disrupt the interaction and the added repression from PLU-1 while retaining basal BF-1 repression. This functional coupling supports transcription corepressor binding for the original Q9UGL1 interaction. The evidence concerns engineered BF-1 constructs and tagged association, with purified affinity unresolved; the separate endogenous experiment concerns PAX9. The assigned activity is binding the corepressor, rather than PLU-1 corepressor or demethylase activity.

Proposed replacements: transcription corepressor binding

Summary: FOXG1 associates with TLE1 in a repression-related nuclear complex.

Reason: Reciprocal endogenous FOXG1/TLE1 co-immunoprecipitation and sequential ChIP at the p21 promoter demonstrate a repression-related association in human BT048 cells (PMID:24356439). TLE knockdown and GRG6 antagonism provide functional context, making transcription corepressor binding more informative than the original generic Q04724 interaction. The evidence establishes co-complex recovery and promoter co-occupancy in tumor cells; binary affinity, stoichiometry and the contact interface remain unresolved.

Proposed replacements: transcription corepressor binding

Summary: FOXG1 acts in the nucleus.

Reason: The positive nucleus IBD at PTN000216104 lies on the exact human FOXG1 lineage, preserving the incoming MGI donor. Human experiments independently support nuclear function: sequence-checked engineered WT EGFP–FOXG1 is nuclear in PMID:21280142, and endogenous FOXG1 occupies promoters in PMID:24356439. The engineered R244C mutant has a distinct speckle phenotype; these constructs are not evidence for natural alternative products.

Summary: The nuclear localization inferred electronically is supported by human experiments.

Reason: The Ensembl/UniProt inference agrees with the retained nuclear IBA and human experiments. WT EGFP–FOXG1 has dispersed nuclear signal excluding nucleoli in PMID:21280142, and endogenous FOXG1 promoter ChIP in PMID:24356439 supports nuclear activity. The engineered R244C speckle phenotype is a separate mutant result; physiological subnuclear distribution can depend on context.

Summary: Reactome places the human FOXG1 input in nucleoplasm.

Reason: The curated R-HSA-9618021 reaction places human FOXG1 entity R-HSA-9022629, mapped to P55316 residues 1–489, in nucleoplasm as a free input and in the FOXO–SMAD complex. Human nuclear localization and endogenous promoter association corroborate this location. Selected original Results and Figure 6C of the model bibliography, PMID:15084259, further show endogenous FOXG1–FOXO3 co-complex recovery in U87MG cells. This supports the modeled association while leaving purified affinity and exclusive nucleoplasmic residence unresolved; complete Experimental Procedures and supplementary material were not inspected.

Summary: Broad transcriptional regulation is covered by the retained Pol II-specific process.

Reason: GO:0006357 is an is_a child of GO:0006355 and is independently supported by human reporter and endogenous transcriptional evidence. The original ARBA/InterPro annotation is retained as source provenance, but the unrestricted parent adds less information than the existing Pol II process. This is a granularity judgment rather than a claim that the electronic mapping is biologically false.

Summary: Regulation of Pol II transcription is an inherited and experimentally supported FOXG1 function.

Reason: The actual PTHR46617 tree/MSA places human FOXG1 below PTN000216104, and the incoming IBA joins its literal positive IBD for GO:0006357 with the original MGI donor unchanged. Human BF-1 reporter repression and endogenous FOXG1/TLE1 promoter occupancy with expression changes independently support this regulatory role. The process remains direction-neutral at this ancestral level; the separate negative-regulation row records the demonstrated repressive context.

Summary: FOXG1 contributes to telencephalon development.

Reason: Refine the broad ARBA process to telencephalon development. Human FOXG1-associated cortical and corpus-callosum abnormalities in PMID:21280142 (clinical Results and Figure 1 caption) provide developmental evidence beyond expression, complemented by the telencephalic expression reported in PMID:7959731 and the established role summarized in PMID:17260156. GO:0021537 is part_of forebrain development, which is part_of brain development. This is a gene-level refinement of the existing developmental assertion; the electronic source and original qualifier remain unchanged.

Proposed replacements: telencephalon development

Summary: FOXG1 contributes to telencephalon development.

Reason: The established FOXG1 developmental role supports the same telencephalon-specific refinement as the other brain-development rows. Independent human clinical evidence in PMID:21280142 links a de novo FOXG1 variant to frontal cortical and corpus-callosum abnormalities; PMID:17260156 places the conserved function in telencephalon development. The original PMID:7599184 TAS identifier is preserved: its accessed abstract supplies developmental expression context, while its full functional assays remain unverified and its historical duplication interpretation is superseded. The refinement does not treat expression alone as participation or certify an unseen assay.

Proposed replacements: telencephalon development

Summary: FOXG1 contributes to telencephalon development.

Reason: Telencephalon development more precisely describes the established FOXG1 developmental role. PMID:7959731 reports telencephalic neuronal expression in human fetal brain and mouse embryos; independent human clinical Results in PMID:21280142 identify frontal cortical and corpus-callosum abnormalities associated with a de novo FOXG1 variant, and PMID:17260156 provides conserved developmental context. The original TAS source remains unchanged, with its exact functional Methods still unverified. The gene-level refinement relies on the combined evidence, rather than treating expression alone as a perturbation assay or historical HFK clone differences as natural products.

Proposed replacements: telencephalon development

Summary: Sequence-specific DNA binding is covered by the existing double-stranded DNA-binding annotations.

Reason: GO:1990837 is an is_a child of GO:0043565. The authentic FOXG1 HT-SELEX rows and the independently traced positive PAINT ancestor support this more specific double-stranded DNA activity. Preserve the original Ensembl/InterPro donor assertions without treating their breadth as a propagation defect. The eDBD construct has two documented old-reference sequence conflicts outside the annotated forkhead domain; this does not establish their effects or a natural product.

Summary: Human FOXG1 can repress transcription driven by a Pol II promoter.

Reason: PMID:12657635 shows repression by GAL4DBD–BF-1 tethered to five GAL4 sites upstream of an adenovirus major late promoter in HEK293 cells, with additional repression upon PLU-1 coexpression. The demonstrated Pol II promoter context supports refinement to GO:0000122. This experiment does not itself test native FOXG1 sequence recognition, and the refinement does not assert that every FOXG1 target or cell state is repressed. Endogenous human FOXG1/TLE1 results provide independent repression-related context.

Proposed replacements: negative regulation of transcription by RNA polymerase II

Summary: FOXG1 inherits sequence-specific double-stranded DNA-binding activity from a supported PAINT ancestor.

Reason: The genuine PTHR46617 tree and MSA place the exact 489-aa human P55316 leaf PTN002483625 below PTN000216104, where a literal positive IBD asserts this activity. The IBD includes P55316 experimental grounding; this is expected descendant evidence, not circular transfer. The incoming row and donor list match the retained PAINT record, with no family negative record. Target-specific HT-SELEX corroborates the activity with its stated construct limits.

Summary: The FOXG1 forkhead-domain construct selects double-stranded DNA motifs.

Reason: The FOXG1 construct selects double-stranded DNA motifs in PMID:28473536 (workbook S2 rows 5118/5123). S1 row 266 identifies FOXG1B and ENSG00000176165. Its 135-aa eDBD best aligns to P55316 residues 163–297 with R281P and R291A, both documented historical sequence conflicts outside the annotated 181–275 forkhead domain. This positive assay supports the existing activity with an explicit construct limitation: exact wild-type identity, effects of the differences and full-length cellular affinity remain unestablished; the engineered fragment is not a natural alternative product.