Set2 methyltransferase facilitates cell cycle progression by maintaining transcriptional fidelity.

Dronamraju R, Jha DK, Eser U, Adams AT, Dominguez D, Choudhury R, Chiang YC, Rathmell WK, Emanuele MJ, Churchman LS, Strahl BD
Nucleic Acids Res. 2018 46 (3): 1331-1344

PMID: 29294086 · PMCID: PMC5814799 · DOI:10.1093/nar/gkx1276

Methylation of histone H3 lysine 36 (H3K36me) by yeast Set2 is critical for the maintenance of chromatin structure and transcriptional fidelity. However, we do not know the full range of Set2/H3K36me functions or the scope of mechanisms that regulate Set2-dependent H3K36 methylation. Here, we show that the APC/CCDC20 complex regulates Set2 protein abundance during the cell cycle. Significantly, absence of Set2-mediated H3K36me causes a loss of cell cycle control and pronounced defects in the transcriptional fidelity of cell cycle regulatory genes, a class of genes that are generally long, hence highly dependent on Set2/H3K36me for their transcriptional fidelity. Because APC/C also controls human SETD2, and SETD2 likewise regulates cell cycle progression, our data imply an evolutionarily conserved cell cycle function for Set2/SETD2 that may explain why recurrent mutations of SETD2 contribute to human disease.

MeSH Terms (18)

Anaphase-Promoting Complex-Cyclosome Biological Evolution Cdc20 Proteins Cell Cycle Gene Expression Regulation, Fungal Histone-Lysine N-Methyltransferase Histones Humans Lysine Methylation Methyltransferases Nocodazole Protein Processing, Post-Translational Proteolysis Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Transcription, Genetic Tubulin Modulators

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