Abstract
Nucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors. Here we show that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 bind preferentially to H3K27ac nucleosomes at cell-type specific chromatin regulatory regions. HMGNs bind directly to the acetylated nucleosome; the H3K27ac residue and linker DNA facilitate the preferential binding of HMGNs to the modified nucleosomes. Loss of HMGNs increases the levels of H3K27me3 and the histone H1 occupancy at enhancers and promoters and alters the interaction of transcription factors with chromatin. These experiments indicate that the H3K27ac epigenetic mark enhances the interaction of architectural protein with chromatin regulatory sites and identify determinants that facilitate the localization of HMGN proteins at regulatory sites to modulate cell-type specific gene expression.
Highlights
Nucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors
Analyses of the genome-wide distribution of HMGN1 and HMGN2 in mouse embryonic stem cells (ESCs) (Fig. 1a, b), resting B cells (Supplementary Fig. 1a) and embryonic fibroblasts (MEFs) (Supplementary Fig. 1b) reveal that both HMGN1 and HMGN2 variants colocalize with H3K27ac, a histone modification that marks enhancers and promoters[7,28,29], but not with H3K27me[3], an epigenetic mark of silent chromatin
We find that in the super-enhancer regions of ESCs, mouse embryonic fibroblasts (MEFs), and resting B cells (rBs) cells, the H3K27ac reads colocalizing with either HMGN1 or HMGN2 are markedly higher that the reads obtained with other epigenetic marks of active chromatin such as H3K9ac, H3K4me[1], H3K64ac, or H3K122ac (Fig. 1c, d, Supplementary Fig. 1c, d, e, f)
Summary
Nucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors. Loss of HMGNs increases the levels of H3K27me[3] and the histone H1 occupancy at enhancers and promoters and alters the interaction of transcription factors with chromatin These experiments indicate that the H3K27ac epigenetic mark enhances the interaction of architectural protein with chromatin regulatory sites and identify determinants that facilitate the localization of HMGN proteins at regulatory sites to modulate cell-type specific gene expression. HMGNs bind to chromatin without DNA sequence specificity, they preferentially localize to enhancers and promoters, chromatin regulatory sites that are digested with DNaseI and enriched in epigenetic marks of active chromatin, including H3K27ac modified histones[21,22].
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