Succinylation of H3K122 destabilizes nucleosomes and enhances transcription

Lara Zorro Shahidian (1) , Mariska Haas (2) , Stéphanie Le Gras (3) , Sandra Nitsch (1) , André Mourão (1) , Arie Geerlof (1) , Raphael Margueron (4) , Jens Michaelis (2) , Sylvain Daujat (3) , Robert Schneider (1, 5, 6)

1 Helmholtz Zentrum München = German Research Center for Environmental Health
2 Universität Ulm - Ulm University [Ulm, Allemagne]
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
4 Génétique et Biologie du Développement
5 DZD - German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg]
6 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München

Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription. Using chromatin succinylated at H3K122 in in vitro transcription assays, we show that the presence of H3K122succ is sufficient to stimulate transcription. In line with this, we found in our ChIP assays H3K122succ enriched on promoters of active genes and H3K122succ enrichment scaling with gene expression levels. Furthermore, we show that the co-activators p300/CBP can succinylate H3K122 and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays, we demonstrate a direct effect of H3K122succ on nucleosome stability, indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the mechanisms underlying transcriptional regulation by H3K122succ.

Mots clés: acylation; histones; succinylation

Domaines: Biochimie, Biologie Moléculaire

Lara Zorro Shahidian, Mariska Haas, Stéphanie Le Gras, Sandra Nitsch, André Mourão, et al.. Succinylation of H3K122 destabilizes nucleosomes and enhances transcription. EMBO Reports, 2021, 22 (3), ⟨10.15252/embr.202051009⟩. ⟨hal-03713626⟩