H3K122succ expands the role of histone acylation in transcriptional regulation
Histone post-translational modifications (PTMs) are key players in chromatin regulation. The recent identification of novel histone acylations raised important questions regarding their role in transcriptional regulation. In this study, we characterized the role of succinylation of H3K122 (H3K122succ), located on the lateral surface of the histone octamer, in transcription and in chromatin function. Using chromatin, site-specifically succinylated at H3K122, we found that the presence of H3K122succ is sufficient to stimulate transcription in vitro. In line with this H3K122succ was enriched on promoters of active genes in mammalian cells and enrichment levels scale with gene expression. Furthermore, we show that the p300 and CBP co-activators are H3K122 succinyltransferases 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 molecular mechanisms of H3K122succ in transcriptional regulation and they highlight a structural function for H3K122succ through direct perturbation of nucleosomes. Overall design: Genome-wide profile of succinylated H3K122 in the human breast cancer MCF7 cell line.