BRD4 is a nuclear BET-family chromatin reader and transcriptional coregulator. Its tandem bromodomains recognize acetylated histones and selected acetylated transcription factors, while its extraterminal region recruits regulatory partners. The long product links regulatory chromatin and transcription factors to P-TEFb, promoting RNA polymerase II elongation, and BRD4 can also recruit effectors through a P-TEFb-independent pathway. These interactions support stimulus-responsive gene expression and the maintenance of transcriptional programs across cell division. Alternative products differ in their C-terminal regions; the studied isoform B recruits condensin II and restricts DNA-damage signaling through chromatin compaction. BRD4 also binds papillomavirus E2 proteins, and BRD4-NUTM1 fusions have oncogenic activities distinct from those of the native protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 functions on acetylated chromatin. Reason: Chromatin association is central to the bromodomain reader mechanism and is independently demonstrated by chromosome localization, histone binding and ChIP experiments. This agrees with the PAINT inference; no independent reconstruction of the ancestral node is claimed. |
| GO:0000794 condensed nuclear chromosome | IDA PMID:10938129 A bromodomain protein, MCAP, associates with mitotic chromos... | ACCEPT | Summary: BRD4/MCAP associates with condensed mitotic chromosomes. Reason: The cited study directly visualizes MCAP on mitotic euchromatin, excluding centromeres, and follows chromosomal association during condensation. The source includes mammalian-cell experiments and anti-MCAP microinjection into human HeLa cells. Keep this established compartment without extrapolating to centromeric or meiotic functions. Supporting Evidence: PMID:10938129 MCAP was absent from centromeres |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:23086925 Bromodomain-containing protein 4 (BRD4) regulates RNA polyme... | MODIFY | Summary: BRD4 occupies regulatory chromatin at active promoters and enhancers. Reason: The inspected Results identify BRD4-bound DNA by ChIP-seq in primary human CD4+ T cells and relate occupancy to acetylated histones and transcription. GO:0000976 specifically asserts binding to a DNA sequence. These experiments establish chromatin association, not direct sequence recognition by BRD4; the mechanistically supported replacement is chromatin binding, already independently represented by other source rows. This is not a claim that BRD4 cannot contact DNA. Proposed replacements: chromatin binding Supporting Evidence: PMID:23086925 We used genome-wide chromatin immunoprecipitation sequencing in primary human CD4+ T cells |
| GO:0002039 p53 binding | IDA PMID:23317504 Phospho switch triggers Brd4 chromatin binding and activator... | ACCEPT | Summary: BRD4 directly binds p53 through regulated interaction regions. Reason: Reciprocal endogenous co-IP, purified-protein mapping and bimolecular fluorescence complementation support BRD4-p53 association. The BID and phosphorylation-dependent PDID regions have different effects on p53 binding to DNA; CK2 phosphorylates BRD4 in this mechanism. Retain p53 binding without assigning p53 DNA-sequence recognition or CK2 catalysis to BRD4. Supporting Evidence: PMID:23317504 endogenous Brd4 associates with endogenous p53 |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 binds chromatin through its bromodomains. Reason: The inherited chromatin-binding assertion is consistent with direct histone recognition and target-specific chromatin occupancy. The target in WITH/FROM is legitimate descendant evidence, not circularity, and no PAINT-node defect is inferred. |
| GO:0003682 chromatin binding | IDA PMID:20871596 Selective inhibition of BET bromodomains. | ACCEPT | Summary: BRD4 bromodomains recognize acetylated chromatin. Reason: The study measures BET bromodomain inhibition, BRD4 structures and cellular displacement from chromatin. The fusion-oncoprotein experiments are explicitly BRD4-NUT context; the biochemical BRD4 bromodomain evidence and independent wild-type studies support the native chromatin-binding assertion. |
| GO:0003712 transcription coregulator activity | IMP PMID:24360279 Brd4 and JMJD6-associated anti-pause enhancers in regulation... | ACCEPT | Summary: BRD4 recruits transcriptional regulators to anti-pause enhancers. Reason: BRD4-dependent JMJD6 recruitment and association with P-TEFb regulate promoter-proximal pause release. Retain transcription coregulator activity. The reported histone/RNA demethylation chemistry belongs to JMJD6 in this model, not to BRD4. Supporting Evidence: |
| GO:0003713 transcription coactivator activity | IMP PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | ACCEPT | Summary: The BRD4 ET domain recruits effectors that support transcriptional activation. Reason: The source reports ET-domain association with NSD3, JMJD6 and GLTSCR1 and their contribution to BRD4-dependent reporter and endogenous-gene activation. This is a coactivator recruitment function separable from C-terminal P-TEFb recruitment; it does not assign the effectors' catalytic activities to BRD4. Supporting Evidence: |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | UNDECIDED | Summary: Intrinsic BRD4 serine/threonine kinase activity remains experimentally disputed. Reason: The original positive report (PMID:22509028) and later mouse-protein assays (PMID:34688663) support intrinsic phosphorylation, whereas an independent study found none with human BRD4 residues 1β698 expressed in E. coli or Sf21 (PMID:24860166). The negative study explicitly allows preparation or activation requirements; it does not establish absence from every human BRD4 form. Species, construct and assay differences remain unresolved. This is not a donor-count, self-source or absent-domain objection. The PAINT node/MSA and donor experiments were not independently reconstructed; the source inference and all supporting entities are preserved. Supporting Evidence: PMID:22509028 directly phosphorylates its serine 2 PMID:24860166 no phosphorylation activity was seen PMID:34688663 WT and tΞC (1β730) efficiently phosphorylated full-length GST-CTD |
| GO:0005515 protein binding | IPI PMID:17023018 Amino acid substitutions that specifically impair the transc... | KEEP AS NON CORE | Summary: The long BRD4 product associates with HPV16 E2 (P03120). Reason: The primary abstract identifies long BRD4 by affinity capture, mass spectrometry and western analysis using viral E2 activation domains; HPV11, HPV31 and CRPV are explicitly named and additional E2 types were tested. Retain the curated exact partner assertion, with subtype coverage for the other E2 construct deferred to the original curator. The binding does not itself establish a general viral-tethering or catalytic function; no current GOA isoform field is invented. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17023018 Amino acid substitutions that specifically impair the transc... | KEEP AS NON CORE | Summary: The long BRD4 product associates with HPV11 E2 (P04015). Reason: The primary abstract identifies long BRD4 by affinity capture, mass spectrometry and western analysis using viral E2 activation domains; HPV11, HPV31 and CRPV are explicitly named and additional E2 types were tested. Retain the curated exact partner assertion, with subtype coverage for the other E2 construct deferred to the original curator. The binding does not itself establish a general viral-tethering or catalytic function; no current GOA isoform field is invented. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17023018 Amino acid substitutions that specifically impair the transc... | KEEP AS NON CORE | Summary: The long BRD4 product associates with HPV31 E2 (P06790). Reason: The primary abstract identifies long BRD4 by affinity capture, mass spectrometry and western analysis using viral E2 activation domains; HPV11, HPV31 and CRPV are explicitly named and additional E2 types were tested. Retain the curated exact partner assertion, with subtype coverage for the other E2 construct deferred to the original curator. The binding does not itself establish a general viral-tethering or catalytic function; no current GOA isoform field is invented. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17023018 Amino acid substitutions that specifically impair the transc... | KEEP AS NON CORE | Summary: The long BRD4 product associates with CRPV E2 (P17383). Reason: The primary abstract identifies long BRD4 by affinity capture, mass spectrometry and western analysis using viral E2 activation domains; HPV11, HPV31 and CRPV are explicitly named and additional E2 types were tested. Retain the curated exact partner assertion, with subtype coverage for the other E2 construct deferred to the original curator. The binding does not itself establish a general viral-tethering or catalytic function; no current GOA isoform field is invented. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17189189 ChlR1 is required for loading papillomavirus E2 onto mitotic... | KEEP AS NON CORE | Summary: BRD4 associates with the curated papillomavirus E2 partner. Reason: The abstract explicitly states that the E2 W130R mutant retains BRD4 binding despite losing ChlR1 binding, chromosome association and episomal maintenance. Thus the interaction is supported but insufficient on its own for viral tethering. Preserve P03122 and the source context; do not transfer ChlR1 helicase activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | UNDECIDED | Summary: The NCK1/P16333 screen interaction needs its target-specific assay. Reason: The accessible abstract describes an SH3-domain peptide-array screen and selected full-length validation, but does not identify the BRD4 peptide or this exact edge. The target-specific matrix and validation were not inspected. Preserve the experimental assertion without assuming every peptide hit is full-length binding or inventing an adaptor function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | UNDECIDED | Summary: The GRB2/P62993 screen interaction needs its target-specific assay. Reason: The accessible abstract describes an SH3-domain peptide-array screen and selected full-length validation, but does not identify the BRD4 peptide or this exact edge. The target-specific matrix and validation were not inspected. Preserve the experimental assertion without assuming every peptide hit is full-length binding or inventing an adaptor function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18305892 Search for cellular partners of human papillomavirus type 16... | KEEP AS NON CORE | Summary: BRD4 binding to HPV16 E2 is retained with source-specific limits. Reason: The cited abstract describes an HPV16 E2 yeast-two-hybrid screen but does not name each recovered partner. The same BRD4-E2 association is explicitly supported by the later mammalian complementation study, including interaction-defective HPV16 E2 controls. Retain the biologically corroborated curated interaction; the original screen edge remains uninspected rather than independently verified. |
| GO:0005515 protein binding | IPI PMID:19103749 Brd4 coactivates transcriptional activation of NF-kappaB via... | MODIFY | Summary: BRD4 recognizes acetylated RelA/NF-kappaB. Reason: Purified bromodomains bind acetyl-Lys310 RelA peptides and acetylated full-length RelA, with cellular interaction and coactivation evidence. NF-kappaB binding identifies the exact Q04206 partner more informatively than generic protein binding; the acetylation dependence is retained in the mechanism. Proposed replacements: NF-kappaB binding Supporting Evidence: PMID:19103749 bromodomains of Brd4 bind to acetylated lysine-310. |
| GO:0005515 protein binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | KEEP AS NON CORE | Summary: BRD4 associates with CHD4/Q14839. Reason: The inspected proteomics and follow-up co-IP Results support association with endogenous BRD4 and ET-containing fragments. These experiments establish complex association rather than purified binary contact for every pair. Retain supported generic binding under the project instruction; no remodeler ATPase, replication-clamp unloading or other partner activity is transferred to BRD4. Supporting Evidence: PMID:21555454 interacts with NSD3, JMJD6, CHD4, GLTSCR1, and ATAD5. |
| GO:0005515 protein binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | KEEP AS NON CORE | Summary: BRD4 associates with ATAD5/Q96QE3. Reason: The inspected proteomics and follow-up co-IP Results support association with endogenous BRD4 and ET-containing fragments. These experiments establish complex association rather than purified binary contact for every pair. Retain supported generic binding under the project instruction; no remodeler ATPase, replication-clamp unloading or other partner activity is transferred to BRD4. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | KEEP AS NON CORE | Summary: BRD4 associates with GLTSCR1/BICRA/Q9NZM4. Reason: The inspected proteomics and follow-up co-IP Results support association with endogenous BRD4 and ET-containing fragments. These experiments establish complex association rather than purified binary contact for every pair. Retain supported generic binding under the project instruction; no remodeler ATPase, replication-clamp unloading or other partner activity is transferred to BRD4. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22645123 Down-regulation of NF-ΞΊB transcriptional activity in HIV-ass... | MODIFY | Summary: BRD4 binds acetylated NF-kappaB/RelA. Reason: The source reports acetyl-Lys310 NF-kappaB recognition by BRD4-BD2, structural/biophysical assays and inhibition of this interaction. Replace the generic term with NF-kappaB binding; the paper's listed erratum has not been independently adjudicated and is not treated as an automatic refutation. Proposed replacements: NF-kappaB binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22761572 Large scale genotype comparison of human papillomavirus E2-h... | KEEP AS NON CORE | Summary: BRD4 associates with the curated HPV16/P03120 E2 protein. Reason: The study tests E2-host interactions in mammalian cells and reports BRD4 binding across most E2 types, with specific HPV16/18 interaction-defective controls. The individual matrix cells for all viral types were not independently inspected; retain the curator's exact partner assignment without claiming complete revalidation of that matrix or sufficiency for viral genome maintenance. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22761572 Large scale genotype comparison of human papillomavirus E2-h... | KEEP AS NON CORE | Summary: BRD4 associates with the curated HPV11/P04015 E2 protein. Reason: The study tests E2-host interactions in mammalian cells and reports BRD4 binding across most E2 types, with specific HPV16/18 interaction-defective controls. The individual matrix cells for all viral types were not independently inspected; retain the curator's exact partner assignment without claiming complete revalidation of that matrix or sufficiency for viral genome maintenance. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22761572 Large scale genotype comparison of human papillomavirus E2-h... | KEEP AS NON CORE | Summary: BRD4 associates with the curated HPV31/P06790 E2 protein. Reason: The study tests E2-host interactions in mammalian cells and reports BRD4 binding across most E2 types, with specific HPV16/18 interaction-defective controls. The individual matrix cells for all viral types were not independently inspected; retain the curator's exact partner assignment without claiming complete revalidation of that matrix or sufficiency for viral genome maintenance. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23455924 A Y2H-seq approach defines the human protein methyltransfera... | KEEP AS NON CORE | Summary: BRD4-JMJD6 association is retained with an uninspected original screen edge. Reason: The cited Y2H-seq abstract does not expose this individual target pair. Independent co-IP and later BRD4 ET-domain/JMJD6 structural experiments establish the same biological association. Retain the curated generic interaction with explicit source deference rather than certifying the original screen or assigning a particular JMJD6 enzymatic reaction to BRD4. |
| GO:0005515 protein binding | IPI PMID:23686307 Brd4 maintains constitutively active NF-ΞΊB in cancer cells b... | MODIFY | Summary: BRD4 directly recognizes acetylated RelA. Reason: The source describes bromodomain/acetyl-RelA structural recognition, binding-defective mutants, cellular co-IP and JQ1 disruption. The exact Q04206 interaction supports NF-kappaB binding; preventing RelA turnover does not make BRD4 a ubiquitin enzyme. Proposed replacements: NF-kappaB binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24360279 Brd4 and JMJD6-associated anti-pause enhancers in regulation... | KEEP AS NON CORE | Summary: BRD4 associates with P-TEFb and JMJD6 during pause release. Reason: The source supports interactions with the CDK9-cyclin T1 complex and JMJD6. All three original partner accessions are preserved. P-TEFb binding is already represented by a separate specific source row; a single replacement covering only CDK9/cyclin T1 would omit JMJD6 from this aggregate. Retain the supported generic assertion without assigning either partner's catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24360279 Brd4 and JMJD6-associated anti-pause enhancers in regulation... | KEEP AS NON CORE | Summary: BRD4 associates with JMJD6 at anti-pause enhancers. Reason: The source supports BRD4-dependent JMJD6 recruitment and their physical association. This is a regulatory interaction; the specific histone/RNA chemistry proposed for JMJD6 is not BRD4 chemistry. Retain the experimentally supported generic association under the task instruction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24525235 Disrupting the interaction of BRD4 with diacetylated Twist s... | MODIFY | Summary: BRD4 recognizes the diacetylated bHLH factor TWIST1. Reason: The abstract and source experiments describe a diacetylated Twist motif engaging BRD4-BD2 while BD1 associates with acetylated H4, assembling transcriptional machinery at WNT5A regulatory chromatin. bHLH transcription factor binding captures Q15672 without turning binding into a general cancer or EMT activity. Proposed replacements: bHLH transcription factor binding Supporting Evidence: PMID:24525235 The diacetylated Twist binds the second bromodomain of BRD4 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | UNDECIDED | Summary: The FAM90A1 screen association requires its exact target record. Reason: The BioPlex abstract describes AP-MS co-association mapping, but the inspected accessible body does not expose this BRD4-FAM90A1 edge. The target row, construct and cell-specific support remain uninspected; no direct binary interaction or molecular mechanism is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29176719 Structural Mechanism of the Oxygenase JMJD6 Recognition by t... | KEEP AS NON CORE | Summary: The BRD4 ET domain associates with JMJD6 and NSD3. Reason: The source combines NMR/ITC analysis of a JMJD6 peptide with full-length BRD4 cellular IP: WT BRD4 associates with JMJD6 and NSD3, while ET deletion or E651A/E653A weakens those associations. The structural peptide and cellular complex assays are distinct. Preserve both partners; do not assign full-length binary affinity from peptide measurements. Supporting Evidence: PMID:29176719 we confirmed the binding of transfected BRD4WT to JMJD6, NSD3 and H4ac |
| GO:0005515 protein binding | IPI PMID:29374058 Glioma tumor suppressor candidate region gene 1 (GLTSCR1) an... | KEEP AS NON CORE | Summary: BRD4 associates with GLTSCR1/BICRA-containing GBAF. Reason: The canonical source body explicitly reports BRD4 IP with GLTSCR1, BRD9 and selected BAF subunits. This supports association, not a BRD4 ATPase activity or permanent membership in every GBAF complex. Retain the exact BICRA partner and the supported generic interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The BRD4-JMJD6 screen association is biologically corroborated. Reason: The BioPlex abstract does not expose this individual edge, but independent target-specific co-IP and structural evidence establish BRD4-JMJD6 binding. Retain the curated generic assertion while distinguishing that corroboration from a fresh inspection of the original BioPlex target row. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The FAM90A1/Q86YD7 interaction lacks an inspected source-specific target assay. Reason: The accessible screen abstract and inspected body do not provide this exact BRD4 interaction. A general description of coactivator interactions or structure predictions does not verify the named target pair. Preserve the source accession and defer the decision pending the target table or validation; no false-binding or wrong-gene claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | UNDECIDED | Summary: The SPDYE4/A6NLX3 interaction lacks an inspected source-specific target assay. Reason: The accessible screen abstract and inspected body do not provide this exact BRD4 interaction. A general description of coactivator interactions or structure predictions does not verify the named target pair. Preserve the source accession and defer the decision pending the target table or validation; no false-binding or wrong-gene claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | UNDECIDED | Summary: The FAM90A1/Q86YD7 interaction lacks an inspected source-specific target assay. Reason: The accessible screen abstract and inspected body do not provide this exact BRD4 interaction. A general description of coactivator interactions or structure predictions does not verify the named target pair. Preserve the source accession and defer the decision pending the target table or validation; no false-binding or wrong-gene claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35182466 Transcription factor protein interactomes reveal genetic det... | MODIFY | Summary: BRD4 associates with the DNA-binding transcription factor GATA4. Reason: The primary Results explicitly identify BRD4 as a GATA4 interactor and state that co-IP validated the association; the interactome was generated in human cardiac progenitors. The more specific transcription-factor-binding term captures P43694. This is coassociation evidence, not proof of a purified binary interface or of every CHD variant's pathogenicity. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:35182466 These CHD candidate genes were detected as GATA4 interactors, which was validated by co-immunoprecipitation |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | KEEP AS NON CORE | Summary: BRD4 associates with wild-type SPOP in a mutation-sensitive interaction. Reason: The Results passage in the fuller authenticated source variant explicitly identifies BRD4 as a WT SPOP partner whose interaction is lost with SPOP F133L; the preserved canonical partial cache omits this passage. Retain the generic association with its WT-versus-mutant boundary; the exact quantitative panel was not reanalyzed. SPOP is a substrate adaptor, so this does not confer ubiquitin-ligase catalysis on BRD4. Supporting Evidence: |
| GO:0005634 nucleus | EXP PMID:16109376 The bromodomain protein Brd4 is a positive regulatory compon... | ACCEPT | Summary: BRD4 acts in nucleus. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 acts in nucleus. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. |
| GO:0005634 nucleus | IDA PMID:20871596 Selective inhibition of BET bromodomains. | ACCEPT | Summary: BRD4 acts in nucleus. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:25593309 Screen identifies bromodomain protein ZMYND8 in chromatin re... | ACCEPT | Summary: BRD4 acts in nucleus. Reason: Nuclear localization is established by independent BRD4 imaging and chromatin studies. The cited bromodomain screen foregrounds ZMYND8; its exact BRD4 image was not inspected, so retain the correct compartment with curator deference rather than asserting the annotation is a paralog error. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: BRD4 acts in nucleus. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: BRD4 acts in nucleoplasm. Reason: Retain the curator-assessed immunofluorescence nucleoplasm localization, consistent with the independently established nuclear reader/coactivator function. The individual source image was not inspected and no subnuclear microdomain beyond the source term is inferred. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9680408 | ACCEPT | Summary: BRD4 acts in nucleoplasm. Reason: The cached Reactome event places BRD4 in nucleoplasm during inhibitor binding or association with CD274 chromatin. This is compatible with established nuclear BRD4 function; the event does not assign drug-target JAK2 catalysis or direct DNA-sequence recognition to BRD4. Supporting Evidence: Reactome:R-HSA-9680408 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9909635 | ACCEPT | Summary: BRD4 acts in nucleoplasm. Reason: The cached Reactome event places BRD4 in nucleoplasm during inhibitor binding or association with CD274 chromatin. This is compatible with established nuclear BRD4 function; the event does not assign drug-target JAK2 catalysis or direct DNA-sequence recognition to BRD4. Supporting Evidence: Reactome:R-HSA-9909635 |
| GO:0005694 chromosome | EXP PMID:16109376 The bromodomain protein Brd4 is a positive regulatory compon... | ACCEPT | Summary: BRD4 acts in chromosome. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. Supporting Evidence: |
| GO:0005694 chromosome | EXP PMID:21890894 Signal-induced Brd4 release from chromatin is essential for ... | ACCEPT | Summary: BRD4 acts in chromosome. Reason: The source follows BRD4 on interphase chromatin and its stimulus-dependent release, followed by association with active P-TEFb. Keep chromosome localization without implying that every BRD4 molecule is permanently chromatin-bound. Supporting Evidence: |
| GO:0005694 chromosome | EXP PMID:23728299 The bromodomain protein Brd4 insulates chromatin from DNA da... | ACCEPT | Summary: BRD4 acts in chromosome. Reason: The primary source demonstrates chromatin association and insulation by the experimentally studied BRD4 isoform B, with condensin II recruitment. Preserve the broad chromosome localization while limiting the DNA-damage phenotype to that product context; no absent GOA isoform field is added. Supporting Evidence: PMID:23728299 by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: BRD4 acts in chromosome. Reason: Nuclear and chromosomal localization are established by BRD4 imaging, chromatin binding and P-TEFb-associated transcriptional function. The source compartment is consistent with that mechanism. Preserve the experimental or curated inference without claiming every product and condition has identical localization. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 contributes to chromatin organization through reader-mediated recruitment. Reason: BRD4 recruits chromatin regulators through its ET domain, associates with GLTSCR1-containing GBAF, and an experimentally studied BRD4 product recruits condensin II. These establish a noncatalytic contribution to chromatin remodeling consistent with the PAINT assertion. They do not establish intrinsic ATP hydrolysis; no donor-count or self-source objection is made. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000117 | ACCEPT | Summary: BRD4 regulates DNA-templated transcription. Reason: The broad electronic assertion is supported by target-specific transcription-factor interactions, chromatin occupancy, coactivator recruitment and gene-expression experiments. Retain the broad term rather than demanding that the ARBA rule encode every product-specific mechanism. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 regulates RNA polymerase II transcription. Reason: This PAINT assertion agrees with direct BRD4 coactivator and pause-release experiments. The source node was not independently reconstructed, but target-specific evidence supports the inherited function; no defect is inferred from donor identities. |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:18039861 Brd4 recruits P-TEFb to chromosomes at late mitosis to promo... | ACCEPT | Summary: BRD4 recruits P-TEFb during late mitosis and early G1. Reason: BRD4 depletion reduces chromosomal recruitment of P-TEFb and expression of growth-associated genes. This supports transcriptional regulation by recruitment rather than requiring BRD4 to phosphorylate Pol II itself. Supporting Evidence: PMID:18039861 Importantly, the recruitment of P-TEFb depends on Brd4. |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IMP PMID:22509028 BRD4 is an atypical kinase that phosphorylates serine2 of th... | UNDECIDED | Summary: The reported intrinsic CTD kinase activity remains unresolved. Reason: The cited 2012 report describes direct CTD phosphorylation. The 2021 study reports CTD phosphorylation by mouse full-length BRD4 and the 1β730 truncation, while the independent 2014 study detected none with human residues 1β698 produced in E. coli or Sf21 and allowed preparation or activation requirements. These experiments differ in species, constructs and assay conditions; the later positive paper also shares investigators with the original report. The conflict leaves intrinsic CTD catalysis unresolved without erasing the curator IMP assertion or reassigning all activity to recruited CDK9. Supporting Evidence: PMID:22509028 directly phosphorylates its serine 2 PMID:24860166 no phosphorylation activity was seen PMID:34688663 WT and tΞC (1β730) efficiently phosphorylated full-length GST-CTD |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:10938129 A bromodomain protein, MCAP, associates with mitotic chromos... | KEEP AS NON CORE | Summary: BRD4/MCAP perturbation impairs G2-to-M progression in the tested cells. Reason: Anti-MCAP antibody microinjection into HeLa nuclei blocks mitotic entry while ongoing DNA replication is not abolished. Retain this contextual cell-cycle regulation as non-core; it is not evidence that BRD4 is itself a cyclin-dependent kinase or the sole G2/M regulator. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | KEEP AS NON CORE | Summary: BRD4 binds the oxygenase JMJD6. Reason: The source reports ET-associated JMJD6 in proteomics and reciprocal/endogenous co-IP experiments. Enzyme binding is supported as a partner role, without choosing among disputed JMJD6 substrate reactions or transferring its catalytic activity to BRD4. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | KEEP AS NON CORE | Summary: BRD4 associates with NSD3 in a transcription-regulatory complex. Reason: The paper identifies endogenous NSD3 association, recruitment and chromatin-methylation effects, while one tagged co-IP uses the short NSD3 isoform. Retain the curator's broad enzyme-binding assertion with this construct limitation; do not claim that the short isoform is catalytic or refine the annotation to an unverified methyltransferase-specific interaction. Supporting Evidence: |
| GO:0032968 positive regulation of transcription elongation by RNA polymerase II | IDA PMID:19103749 Brd4 coactivates transcriptional activation of NF-kappaB via... | ACCEPT | Summary: BRD4 recruits CDK9 to facilitate NF-kappaB-dependent transcription elongation. Reason: The source links acetyl-RelA recognition to BRD4/CDK9 recruitment and transcriptional output. This is a direct recruitment/coactivator contribution to elongation; CDK9 performs the assigned phosphorylation in this mechanism. Supporting Evidence: |
| GO:0032968 positive regulation of transcription elongation by RNA polymerase II | IMP PMID:18039861 Brd4 recruits P-TEFb to chromosomes at late mitosis to promo... | ACCEPT | Summary: BRD4-mediated P-TEFb recruitment supports productive elongation. Reason: The source shows late-mitotic P-TEFb recruitment and BRD4-dependent transcription of G1 genes. Retain positive regulation of elongation, distinguishing the BRD4 recruiting factor from the P-TEFb kinase. Supporting Evidence: |
| GO:0042393 histone binding | IBA GO_REF:0000033 | ACCEPT | Summary: BRD4 binds histones as part of its chromatin-reader mechanism. Reason: The broad PAINT histone-binding assertion is directly corroborated by acetylated-histone recognition. Retain the broad source assertion alongside the independently curated specific reader rows; duplicate biological coverage does not invalidate a phylogenetic inference. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:19103749 Brd4 coactivates transcriptional activation of NF-kappaB via... | KEEP AS NON CORE | Summary: BRD4 coactivates the nuclear NF-kappaB transcriptional response. Reason: The source directly links BRD4 acetyl-RelA binding to expression of a subset of inflammatory NF-kappaB target genes. Retain the contextual positive-regulation annotation at the nuclear transcriptional stage; it does not assert BRD4 activates upstream receptor/IKK chemistry. Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:21555454 The Brd4 extraterminal domain confers transcription activati... | ACCEPT | Summary: BRD4 recruits ET-domain effectors to activate transcription. Reason: Target-gene and reporter experiments support BRD4-dependent activation by recruited NSD3, JMJD6 and GLTSCR1. This is regulation of transcription, not an assertion that BRD4 polymerizes RNA or performs the partners' enzymatic reactions. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:23086925 Bromodomain-containing protein 4 (BRD4) regulates RNA polyme... | ACCEPT | Summary: BRD4 supports Pol II transcription at active T-cell regulatory chromatin. Reason: The source combines primary human CD4+ T-cell ChIP-seq, transcript measurements and bromodomain inhibition. BRD4 occupancy and Pol II Ser2-associated output support the regulatory function. JQ1 is a BET inhibitor, so these experiments alone do not uniquely prove an intrinsic BRD4 kinase mechanism. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:23317504 Phospho switch triggers Brd4 chromatin binding and activator... | ACCEPT | Summary: Regulated BRD4-p53 association promotes target-gene transcription. Reason: The study maps direct p53 binding, CK2-controlled BRD4 chromatin association and p53 target-gene output. Keep positive regulation of Pol II transcription without transferring p53 sequence recognition or CK2 kinase activity to BRD4. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:24360279 Brd4 and JMJD6-associated anti-pause enhancers in regulation... | ACCEPT | Summary: BRD4-JMJD6 enhancer recruitment promotes Pol II pause release. Reason: The source supports BRD4 recruitment and interaction with P-TEFb during activation of coding genes. BRD4 contributes regulatory assembly; the specific demethylation/decapping chemistry proposed in the paper is not attributed to BRD4. Supporting Evidence: |
| GO:0050727 regulation of inflammatory response | IDA PMID:19103749 Brd4 coactivates transcriptional activation of NF-kappaB via... | KEEP AS NON CORE | Summary: BRD4 modulates inflammatory gene expression through acetyl-RelA recognition. Reason: The source uses inflammatory stimuli and BRD4 perturbation to connect its reader/coactivator function to a subset of NF-kappaB-responsive genes. Retain this cell-context-dependent outcome as non-core, without inferring universal inflammatory activation in every tissue. Supporting Evidence: |
| GO:0099122 RNA polymerase II C-terminal domain binding | IDA PMID:22509028 BRD4 is an atypical kinase that phosphorylates serine2 of th... | ACCEPT | Summary: BRD4 physically interacts with the RNA polymerase II CTD. Reason: CTD physical interaction is supported by purified-protein pull-down and cellular co-IP and is logically independent of disputed catalysis. Keep the specific binding source assertion; this consultation does not prescribe a separate redundant core. Supporting Evidence: |
| GO:0106140 P-TEFb complex binding | IDA PMID:24360279 Brd4 and JMJD6-associated anti-pause enhancers in regulation... | ACCEPT | Summary: BRD4 binds the P-TEFb transcription elongation complex. Reason: Physical association with CDK9/cyclin T1 and recruitment during pause release support this specific complex-binding activity. Binding and activation of P-TEFb do not make BRD4 the enzyme catalyzing every Pol II phosphorylation event. Supporting Evidence: PMID:24360279 The interactions of both JMJD6 and Brd4 with the P-TEFb complex permit its activation and pause release of regulated coding genes. |
| GO:0140008 histone H4 reader activity | IDA PMID:20871596 Selective inhibition of BET bromodomains. | ACCEPT | Summary: BRD4 recognizes acetylated H4 and links chromatin to regulatory proteins. Reason: BRD4 bromodomain structural and competition experiments establish acetyl-lysine recognition, and independent wild-type chromatin/recruitment studies support the reader role. Keep native H4 reading distinct from the disease phenotypes of BRD4-NUT fusion cells. |
| GO:0140008 histone H4 reader activity | IDA PMID:23086925 Bromodomain-containing protein 4 (BRD4) regulates RNA polyme... | ACCEPT | Summary: BRD4 recognizes acetylated H4 and links chromatin to regulatory proteins. Reason: The source links acetylated-H4-rich chromatin to BRD4 occupancy, Pol II Ser2 and gene expression in primary human CD4+ T cells. This is interpreted with independent biochemical H4 recognition, not as if ChIP co-occurrence alone measured a unique mark-specific affinity. |
| GO:0140008 histone H4 reader activity | IDA PMID:23317504 Phospho switch triggers Brd4 chromatin binding and activator... | ACCEPT | Summary: BRD4 recognizes acetylated H4 and links chromatin to regulatory proteins. Reason: The paper assays BRD4 binding to acetylated chromatin/histones, regulation by an intramolecular phospho-switch and target-gene recruitment. These establish the reader/coactivator mechanism rather than isolated histone affinity. Supporting Evidence: |
| GO:0140008 histone H4 reader activity | IDA PMID:29176719 Structural Mechanism of the Oxygenase JMJD6 Recognition by t... | ACCEPT | Summary: BRD4 recognizes acetylated H4 and links chromatin to regulatory proteins. Reason: The source's full-length BRD4 IP associates WT and ET-mutant proteins with acetylated H4; ET deletion disrupts effector interactions while leaving H4 association. Independent chromatin-recruitment studies establish the broader reader role. This source does not specify a single acetylated H4 residue. |
| GO:0140011 histone H4K12ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | UNDECIDED | Summary: The BRD4 reader mechanism is established, but the exact H4K12ac result in this source remains unverified. Reason: PMID:29379197 assays purified human BRD4 bromodomains on histone peptide arrays and connects impaired acetyl-histone recognition to chromatin recruitment. However, the accessible text does not resolve the H4K12ac-specific array result; the mark-by-mark Fig.2A display was not retrieved. Retain the curated IDA assertion as UNDECIDED at this access boundary, without claiming it is biologically incorrect or replacing it with another mark. Supporting Evidence: |
| GO:0140012 histone H4K5ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | UNDECIDED | Summary: The BRD4 reader mechanism is established, but the exact H4K5ac result in this source remains unverified. Reason: PMID:29379197 assays purified human BRD4 bromodomains on histone peptide arrays and connects impaired acetyl-histone recognition to chromatin recruitment. However, the accessible text does not resolve the H4K5ac-specific array result; the mark-by-mark Fig.2A display was not retrieved. Retain the curated IDA assertion as UNDECIDED at this access boundary, without claiming it is biologically incorrect or replacing it with another mark. Supporting Evidence: |
| GO:0140046 histone H4K16ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | UNDECIDED | Summary: The BRD4 reader mechanism is established, but the exact H4K16ac result in this source remains unverified. Reason: PMID:29379197 assays purified human BRD4 bromodomains on histone peptide arrays and connects impaired acetyl-histone recognition to chromatin recruitment. However, the accessible text does not resolve the H4K16ac-specific array result; the mark-by-mark Fig.2A display was not retrieved. Retain the curated IDA assertion as UNDECIDED at this access boundary, without claiming it is biologically incorrect or replacing it with another mark. Supporting Evidence: |
| GO:0140055 histone H4K8ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | UNDECIDED | Summary: The BRD4 reader mechanism is established, but the exact H4K8ac result in this source remains unverified. Reason: PMID:29379197 assays purified human BRD4 bromodomains on histone peptide arrays and connects impaired acetyl-histone recognition to chromatin recruitment. However, the accessible text does not resolve the H4K8ac-specific array result; the mark-by-mark Fig.2A display was not retrieved. Retain the curated IDA assertion as UNDECIDED at this access boundary, without claiming it is biologically incorrect or replacing it with another mark. H4K8ac appears in the immunoblot Methods, but that alone does not establish its result. Supporting Evidence: |
| GO:0140072 histone H3K9ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | ACCEPT | Summary: BRD4 recognizes H3K9ac within its acetylated-chromatin reader role. Reason: The paper explicitly reports reduced association with H3K9ac after the disease-associated bromodomain mutation in mouse embryonic stem cells, alongside purified human bromodomain peptide-array assays and reduced mutant chromatin occupancy. This supports the curated reader annotation and the broader recruitment mechanism. The mark-specific cellular experiment is mouse, not a directly re-read human full-length affinity assay; no exclusive recognition or numerical affinity is claimed. Supporting Evidence: |
| GO:0140119 histone H3K27ac reader activity | IDA PMID:29379197 BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia ... | ACCEPT | Summary: BRD4 recognizes H3K27ac within its acetylated-chromatin reader role. Reason: The paper explicitly reports reduced association with H3K27ac after the disease-associated bromodomain mutation in mouse embryonic stem cells, alongside purified human bromodomain peptide-array assays and reduced mutant chromatin occupancy. This supports the curated reader annotation and the broader recruitment mechanism. The mark-specific cellular experiment is mouse, not a directly re-read human full-length affinity assay; no exclusive recognition or numerical affinity is claimed. Supporting Evidence: |
| GO:2000330 positive regulation of T-helper 17 cell lineage commitment | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific Th17-lineage transfer remains incompletely traced. Reason: The ISS assertion names mouse Q9ESU6. BRD4 transcriptional regulation is well established, but the exact donor experiment supporting positive Th17 lineage commitment has not been recovered in the inspected source set. Preserve the curator transfer and donor identifier while leaving this specific developmental claim unresolved; mouse origin alone is not a reason to reject it. |
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Download this section (compressed HTML)Q: Which human BRD4 preparations and activation states account for the positive and negative intrinsic kinase assays, and can clean separation-of-function mutants distinguish BRD4 catalysis from recruited kinases?
Q: How do the intrinsic histone acetyltransferase activity reported in PMID:27159561 and p300-dependent acetylation contributions separate under endogenous human conditions, considering the reported biochemical controls and the corrected Figure 2c?
Q: Can the individual H4-mark peptide-array results in the curated reader source be inspected alongside nucleosome-context and full-length recruitment assays?
Q: How do the three named BRD4 products partition ET-mediated regulation, P-TEFb recruitment and condensin-II-associated chromatin insulation?
Q: Which exact mouse experiment underlies the curated Th17-lineage ISS transfer, and how directly does its mechanism extend to human BRD4?
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