G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation

35Citations
Citations of this article
58Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Differentiation of skeletal muscle cells, like most other cell types, requires a permanent exit from the cell cycle. The epigenetic programming underlying these distinct cellular states is not fully understood. In this study, we provide evidence that the lysine methyltransferase G9a functions as a central axis to regulate proliferation and differentiation of skeletal muscle cells. Transcriptome analysis of G9a knockdown cells revealed deregulation of many cell cycle regulatory genes. We demonstrate that G9a enhances cellular proliferation by two distinct mechanisms. G9a blocks cell cycle exit via methylation-dependent transcriptional repression of the MyoD target genes p21Cip/Waf1 and Rb1. In addition, it activates E2F1-target genes in a methyltransferase activity-independent manner. We show that G9a is present in the E2F1/PCAF complex, and enhances PCAF occupancy and histone acetylation marks at E2F1-target promoters. Interestingly, G9a preferentially associates with E2F1 at the G1/S phase and with MyoD at the G2/M phase. Our results provide evidence that G9a functions both as a co-activator and a co-repressor to enhance cellular proliferation and inhibit myogenic differentiation.

Cite

CITATION STYLE

APA

Rao, V. K., Ow, J. R., Shankar, S. R., Bharathy, N., Manikandan, J., Wang, Y., & Taneja, R. (2016). G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation. Nucleic Acids Research, 44(17), 8129–8143. https://doi.org/10.1093/nar/gkw483

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free