The NSD2/WHSC1/MMSET methyltransferase prevents cellular senescence-associated epigenomic remodeling.

ABSTRACT: Senescent cells may possess the intrinsic programs of metabolic and epigenomic remodeling, but the molecular mechanism remains to be clarified. Using an RNAi-based screen of chromatin regulators, we found that knockdown of the NSD2/WHSC1/MMSET methyltransferase induced cellular senescence that augmented mitochondrial mass and oxidative phosphorylation in primary human fibroblasts. Transcriptome analysis showed that loss of NSD2 downregulated the expression of cell cycle-related genes in a retinoblastoma protein (RB)-mediated manner. Chromatin immunoprecipitation analyses further revealed that NSD2 was enriched at the gene bodies of actively transcribed genes, including cell cycle-related genes, and that loss of NSD2 decreased the levels of histone H3 lysine 36 trimethylation (H3K36me3) at

SUBMITTER: Tanaka H 

PROVIDER: S-EPMC7433007 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature