Acetylation of Histone H3 Lysine 56 Abolishes Linker Histone Regulation of Transcription Factor Binding

Abstract

The linker histone H1 is an ubiquitous regulator of chromatin structure and dynamics. These linker histones are highly abundant in metazoan somatic cells with almost one linker histone per nucleosome, and regulate gene expression during development and within somatic cells. We used fluorescence resonance energy transfer (FRET) to detect changes to nucleosome wrapping, which is sensitive to both H1 binding and transcription factor binding within the nucleosome. H1 binding induces an increase in nucleosome wrapping and FRET, while transcription factor binding within the nucleosome decreases nucleosome wrapping and FRET. We find that H1 suppresses but does not abolish TF binding suggesting that H1 dynamically regulates nucleosomal DNA accessibility to TF binding. We then prepared nucleosomes with histone H3 acetylated at lysine 56 (H3K56ac). This modification is involved transcriptional regulation and increases DNA unwrapping. We find that this modification abolishes H1 suppression of TF binding within the nucleosome. This result suggests that H3K56ac can encode, within a nucleosome, H1 regulation of DNA accessibility and provides a mechanism by which H1 regulation of DNA accessibility is targeted through the genome.