HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers [ATAC-Seq]
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. Overall design: ATAC-seq data for R1-AD1 FLAG-HA-H3F3A (WT androgen receptor) prostate cancer cells and its derivatives (AR KO, HIRA KO, DAXX KO)