Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic Stem Cells

Aster H. Juan, Stan Wang, Kyung Dae Ko, Hossein Zare, Pei Fang Tsai, Xuesong Feng, Karinna O. Vivanco, Anthony M. Ascoli, Gustavo Gutierrez-Cruz, Jordan Krebs, Simone Sidoli, Adam L. Knight, Roger A. Pedersen, Benjamin A. Garcia, Rafael Casellas, Jizhong Zou, Vittorio Sartorelli

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The polycomb repressive complex 2 (PRC2) methylates lysine 27 of histone H3 (H3K27) through its catalytic subunit Ezh2. PRC2-mediated di- and tri-methylation (H3K27me2/H3K27me3) have been interchangeably associated with gene repression. However, it remains unclear whether these two degrees of H3K27 methylation have different functions. In this study, we have generated isogenic mouse embryonic stem cells (ESCs) with a modified H3K27me2/H3K27me3 ratio. Our findings document dynamic developmental control in the genomic distribution of H3K27me2 and H3K27me3 at regulatory regions in ESCs. They also reveal that modifying the ratio of H3K27me2 and H3K27me3 is sufficient for the acquisition and repression of defined cell lineage transcriptional programs and phenotypes and influences induction of the ESC ground state.

Original languageEnglish (US)
Pages (from-to)1369-1382
Number of pages14
JournalCell Reports
Volume17
Issue number5
DOIs
StatePublished - Oct 25 2016
Externally publishedYes

Keywords

  • embryonic stem cells
  • H3K27 methylation
  • polycomb proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Juan, A. H., Wang, S., Ko, K. D., Zare, H., Tsai, P. F., Feng, X., Vivanco, K. O., Ascoli, A. M., Gutierrez-Cruz, G., Krebs, J., Sidoli, S., Knight, A. L., Pedersen, R. A., Garcia, B. A., Casellas, R., Zou, J., & Sartorelli, V. (2016). Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic Stem Cells. Cell Reports, 17(5), 1369-1382. https://doi.org/10.1016/j.celrep.2016.09.087