| 2022 |
BRD8 maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex, creating a repressive chromatin state that prevents p53 transactivation and sustains proliferation in TP53-wild-type GBM. Targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility, and engages p53 transactivation, enforcing cell cycle arrest. |
ChIP, chromatin accessibility assays, bromodomain inhibition/targeting, loss-of-function in patient-derived GBM models, gene expression analysis |
Nature |
High |
36544023
|
| 2012 |
BRD8, as a subunit of the p400 complex, promotes adipogenesis by targeting and incorporating histone variant H2A.Z into transcriptional regulatory regions of PPARγ target genes; shRNA knockdown of Brd8 blocks H2A.Z incorporation, PPARγ accumulation, p400 and RNA Pol II recruitment, and abrogates fat cell differentiation. |
shRNA knockdown, chromatin immunoprecipitation (ChIP), lipid accumulation assays in 3T3-L1 preadipocytes |
Endocrinology |
High |
23064015
|
| 2009 |
BRD8 is an accessory subunit of the human NuA4-HAT (TRRAP/TIP60) complex and confers resistance to spindle poisons; siRNA knockdown of BRD8 induces cell death/growth delay in colorectal cancer lines and sensitizes surviving cells to spindle poisons and proteasome inhibitor MG132, while overexpression of at least one BRD8 isoform confers growth advantage and taxol resistance. |
siRNA knockdown, stable overexpression in HeLa cells, cell viability assays, expression cloning |
International journal of oncology |
Medium |
19787264
|
| 2018 |
Knockdown of BRD8 activates the p53 transcriptional pathway, upregulating p21 and pro-apoptotic genes, inducing G1/S arrest and apoptosis. BRD8 depletion also triggers the DNA damage response (DDR) under normal growth conditions, activating ATM-CHK2 signaling, reducing CHK1, inducing replication stress (enhanced RPA32 phosphorylation), and reducing H4K16 acetylation, suggesting BRD8 is required for p400/Tip60 complex recruitment/stabilization at chromatin for DNA repair. |
siRNA knockdown, flow cytometry (cell cycle/apoptosis), Western blot (p21, CHK1/2, RPA32 phosphorylation, H4K16ac), DNA damage foci detection |
Scientific reports |
Medium |
30237520
|
| 2023 |
BRD8 protein accumulates in colorectal cancer cells through inhibition of ubiquitin-dependent degradation via interaction with MRG domain binding protein. BRD8 transactivates genes independently of TIP60, regulates multiple subunits of the pre-replicative complex in concert with activator protein-1 (AP-1), and its bromodomain is indispensable for interaction with histone H4, transcriptional regulation, and its own protein stability. BRD8 depletion causes G1 cell cycle arrest. |
Transcriptome analysis, genome-wide BRD8 ChIP-seq, co-immunoprecipitation, bromodomain mutagenesis, siRNA knockdown, cell cycle analysis |
iScience |
High |
37123243
|
| 2021 |
A chemoproteomics approach using a functionalized BRD9 ligand affinity matrix identified BRD8 as a bromodomain-containing subunit of the NuA4 complex; selective and cellularly active first-in-class small molecule probes for BRD8 were developed using homology-model-guided design. |
Chemoproteomics (affinity matrix pulldown/MS), homology model-guided probe design, cellular activity assays |
ACS chemical biology |
Medium |
34515462
|
| 2020 |
BRD8 knockdown reduces KAT5 (TIP60) protein levels and expression of KAT5-induced genes in HCC cells, placing BRD8 upstream of KAT5 in regulating HCC cell proliferation and apoptosis resistance. miR-876-3p directly targets BRD8 mRNA (confirmed by luciferase reporter assay), negatively regulating BRD8 expression. |
siRNA knockdown, overexpression, luciferase reporter assay, Western blot, RT-qPCR, cell viability and apoptosis assays |
Archives of biochemistry and biophysics |
Medium |
32860757
|
| 2021 |
BRD8 occupies genome-wide sites in human lung epithelial cells, co-occupying regions with CTCF. BRD8 depletion increases secretion of beta-defensin 1 and multiple chemokines and reduces cell proliferation, implicating BRD8 in regulation of innate immune response genes and the cell cycle. |
ChIP-seq (genome-wide BRD8 occupancy), siRNA depletion, gene expression analysis, motif over-representation analysis, cytokine/peptide secretion assays |
Molecular and cellular endocrinology |
Medium |
33476703
|
| 2024 |
BRD8 reads histone acetylation to localize the histone acetyltransferase KAT5 genome-wide; BRD8 maintains open chromatin at somatic genes and histone acetylation at naive-specific genes in primed mouse epiblast stem cells, thereby impeding conversion to naive ESCs. Reduction of Brd8 reduces histone acetylation at naive-specific genes and permits faster acquisition of accessible chromatin at those loci during cell type conversion. |
ATAC-seq, ChIP-seq (histone acetylation), Brd8 knockdown/depletion, cell type conversion assays (EpiSC to naive ESC), chromatin accessibility analysis |
Advanced science |
High |
39656858
|
| 2026 |
BRD8, as an acetyl-lysine reader in the EP400 complex, mediates ER/HER2 signaling crosstalk in HR+/HER2+ breast cancer. BRD8 expression increases after anti-HER2 treatment; its depletion disrupts ER-HER2 interaction and enhances drug sensitivity. BRD8 regulates chromatin opening (H2AZac deposition via EP400) at ER, FOX, and ETS transcription factor motif-containing regions after anti-HER2 treatment, and is required for neratinib-induced ER activation. |
Single-cell transcriptomics, single-nucleus ATAC-seq, BRD8 depletion, co-immunoprecipitation (ER-HER2), H2AZac ChIP, drug sensitivity assays, clinical trial validation |
Cancer research |
High |
41886605
|
| 2025 |
BRD8 knockdown suppresses TGF-β1 upregulation, which in turn reduces M2-like tumor-associated macrophage (TAM2) polarization and decreases migration and invasion of colorectal cancer cells, placing BRD8 upstream of TGF-β1 in regulating the tumor immune microenvironment. |
siRNA knockdown, RT-qPCR, Western blot, flow cytometry (macrophage polarization), transwell migration/invasion assays, IHC/immunofluorescence |
Discover oncology |
Low |
40720004
|