Herein we uncover a relationship between histone succinylation and Jumonji (JmjC) domain-containing histone demethylases. We used quantitative proteomics and peptide pull-down assays to identify JmjC demethylases as candidate interactors with succinylated histone peptides. Succinyl-lysine peptides bind and inhibit the catalytic activity of JmjC demethylases in a dose-dependent manner. This includes KDM4D and KDM6B, which are responsible for the removal of the silencing marks H3K9me2/3 and H3K27me2/3. Supraphysiological sodium succinate treatment of HepG2/C3A cells increased the relative abundance of histone succinylation, H3K9me2/3, and H3K27me2/3. CUT&Tag and ChIP-mass spectrometry revealed the co-occurrence of succinylation with these repressive methylation marks, in addition to reduced transcriptional output. This work establishes a novel mechanistic link between metabolite abundance and chromatin regulation and suggests a role for histone succinylation in the maintenance of heterochromatin.
Graff, S., Stransky, S., Kraz, I., Duraivelan, K., Poppel, A. J., Chatoff, A., Snyder, N. W., Garforth, S. J., Shechter, D., Maianti, J. P., Sidoli, S.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 7
- Comments 0