Histone 3 lysine 56 acetylation (H3K56ac) regulates extrachromosomal DNA (ecDNA) hub maintenance.

ABSTRACT: Extrachromosomal DNAs (ecDNAs) play an important role in tumor progression. ecDNA hubs have been shown to be anchored by BRD4, a chromatin reader. However, the chromatin organization of ecDNA hub remains unknown. Here we show that histone 3 lysine 56 acetylation (H3K56ac) mark binds to BRD4 specifically. Knockdown of BRD4 decreased the ecDNA hub signals by the ecTag method. Knockdown of an epigenetic player (USP7), histone acetyltransferase (CBP), or histone chaperone (Asf1a) that regulates H3K56ac mark also decreased ecDNA hub signals and H3K56ac levels, supporting the role of H3K56ac in regulating ecDNA hub maintenance. Co-immunoprecipitation experiments showed the interactions of BRD4, USP7, Asf1a, and CBP. Analysis of ChIP-seq datasets showed that both H3K56ac and H3K27ac converged wit

SUBMITTER: Liao LZ 

PROVIDER: S-EPMC12808529 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature