Replication-independent nucleosome turnover confers the functional basis of cis-regulatory elements in adult heart

Through integrated H2BGFP ChIP-seq data over multiple conditions and time points, as well as other related ChIP-seq and RNA-seq data in adult mouse heart. We observed genomewide and locus-specific H2B turnover in non-proliferating adult cardiomyocytes (Cms), and a majority of genomic regions with rapid turnover rates distributes on cis-regulatory elements, as well as these regions are associated with heart function, regulatory factors binding and their activities. Moreover, H2B turnover rate is always positively correlated with gene transcription level on enhancers, promoters and exons. The rapid turnover rates at cis-regulatory elements can be partially explained by the binding and co-binding of RNAP II and various transcription factors (TFs). Our further analysis revealed that not only rapid H2B turnover at cis-regulatory elements responses to heart disease, but also slow turnover at H3K27me3 sites functionally responses to heart disease with a different manner. More generally, we indicate that the binding and co-binding of DNA-binding proteins, such as TFs and epigenetic enzymes, all of them coupled with H2B turnover to modulate gene transcription and chromatin state. Profile H2BGFP occupancy in isolated adult cardiomyocytes from Wildtype (WT), cardiac conditional EED Knockout (CKO), and TAC mice at multiple time points.