Interactome of Site-Specifically Acetylated Linker Histone H1

• Published in: Journal of proteome research Vol. 20; no. 9; pp. 4443 - 4451
• Main Authors: Höllmüller, Eva, Greiner, Katharina, Kienle, Simon M, Scheffner, Martin, Marx, Andreas, Stengel, Florian
• Format: Journal Article
• Language: English
• Published: American Chemical Society 03-09-2021
• Subjects: acetylation; linker histone H1; histone code; genetic code expansion; post-translational modification; affinity purification mass spectrometry; chromatin; protein−protein interactions; epigenetics
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.1c00396

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.