Interactome of Site-Specifically Acetylated Linker Histone H1

Linker histone H1 plays a key role in chromatin organization and maintenance, yet our knowledge of the regulation of H1 functions by post-translational modifications is rather limited. In this study, we report on the generation of site-specifically mono- and di-acetylated linker histone H1.2 by genetic code expansion. We used these modified histones to identify and characterize the acetylation-dependent cellular interactome of H1.2 by affinity purification mass spectrometry and show that site-specific acetylation results in overlapping but distinct groups of interacting partners. Among these, we find multiple translational initiation factors and transcriptional regulators such as the NAD(+)-dependent deacetylase SIRT1, which we demonstrate to act on acetylated H1.2. Taken together, our data suggest that site-specific acetylation of H1.2 plays a role in modulating proteinprotein interactions.

Automated summary

Linker histone H1 plays a key role in chromatin organization and maintenance. Using site-specifically mono- and di-acetylated linker histone H1.2 generated by genetic code expansion, this study identified and characterized the acetylation-dependent cellular interactome of H1.2, demonstrating a role in modulating protein-protein interactions. Among the interacting partners identified are translational initiation factors and transcriptional regulators.