INO80 / SWR remodelers regulate Pol II transcription through BRD2 and chromatin landscape (ChAR-Seq)

INO80 / SWR remodelers, including INO80, P400 / TIP60, and SR CAP, ha v e been vie w ed to regulate H2A.Z dynamics, but how they control specific gene expression remains unclear. Here, we reveal distinct phenotypes arising from short- and long-term perturbations f ollo wing the depletion of INO80 / SWR remodelers. We identified the direct target genes of INO80, P400, and SRCAP remodelers. Mechanistically, we found that INO80 / SWR remodelers interact and facilitate the chromatin occupancy of the H2A.Zac reader protein BRD2, thereby elucidating the regulation of Pol II transcription b y INO80 / SWR remodelers. A dditionally, while the degradation of P400 or SRCAP led to a reduction in H2A.Zac, INO80 depletion did not affect H2A.Zac occupancy but decreased the occupancy of P400 and SRCAP. Collectively, our findings suggest that INO80 / SWR remodelers primarily regulate the chromatin landscape and influences BRD2 chromatin binding, thereby shedding light on their mechanisms in Pol II transcription regulation during de v elopment and disease. We performed ChIP-Seq, Cut&Tag, ATAC-Seq, ChAR-Seq and RNA-Seq to investigate the functions of INO80/SWR remodelers.