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 protein–protein
interactions.