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HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230744 | GEO | 2023/11/02

REPOSITORIES: GEO

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HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers.

Project description:Incorporation of histone variant H3.3 comprises active territories of chromatin. Exploring the function of H3.3 in prostate cancer (PC), we found that knockout (KO) of H3.3 chaperone HIRA suppresses PC growth in vitro and in xenograft settings, deregulates androgen-induced gene expression and alters androgen receptor (AR) binding within enhancers of target genes. H3.3 affects transcription in multiple ways, including activation of p300 by phosphorylated H3.3 at Ser-31 (H3.3S31Ph), which results in H3K27 acetylation (H3K27Ac) at enhancers. In turn, H3K27Ac recruits bromodomain protein BRD4 for enhancer-promoter interaction and transcription activation. We observed that HIRA KO reduces H3.3 incorporation, diminishes H3.3S31Ph and H3K27Ac, modifies recruitment of BRD4. These results suggest that H3.3-enriched enhancer chromatin serves as a platform for H3K27Ac-mediated BRD4 recruitment, which interacts with and retains AR at enhancers, resulting in transcription reprogramming. In addition, HIRA KO deregulates glucocorticoid- (GR) driven transcription of genes co-regulated by AR and GR, suggesting a common H3.3/HIRA-dependent mechanism of nuclear receptors function. Expression of HIRA complex proteins is increased in PC compared with normal prostate tissue, especially in high-risk PC groups, and is associated with a negative prognosis. Collectively, our results demonstrate function of HIRA-dependent H3.3 pathway in regulation of nuclear receptors activity.

| S-EPMC10602887 | biostudies-literature

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [RNA-Seq]

Project description:To study the function of histone variant H3.3 pathway in androgen receptor-driven transcription in prostate cancer (PCa) we knocked out androgen receptor (AR) and H3.3 chaperones HIRA and DAXX in R1-AD1 (wild type AR) and R1-D567 (deltaLBD AR) cell lines. Integrative analysis with RNA-seq, ChIP-seq and ATAC-seq revealed that HIRA KO deregulates androgen-induced gene expression in PCa by reducing H3.3 incorporation, diminishing H3.3S31Ph and H3K27Ac, thus modifying recruitment of BRD4 and altering AR binding within enhancers of target genes.

2023-11-02 | GSE230741 | GEO

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ChIP-Seq]

2023-11-02 | GSE230740 | GEO

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ATAC-Seq]

2023-11-02 | GSE230529 | GEO

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [Dex RNA-seq]

Project description:To study the function of histone variant H3.3 pathway in prostate cancer (PCa) we knocked out androgen receptor (AR) and H3.3 chaperones HIRA and DAXX in R1-AD1 FLAG-HA-H3F3A cell line. We analyzed the effect of Dexamethasone treatment on the transcriptome in these four cell lines.

2023-11-02 | GSE237803 | GEO

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers

Project description:HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers

| PRJNA962494 | ENA

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ATAC-Seq]

Project description:HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ATAC-Seq]

| PRJNA961713 | ENA

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [RNA-Seq]

Project description:HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [RNA-Seq]

| PRJNA962501 | ENA

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ChIP-Seq]

Project description:HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ChIP-Seq]

| PRJNA962502 | ENA

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [Dex RNA-seq]

Project description:HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [Dex RNA-seq]

| PRJNA996638 | ENA

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