H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm

Yuanliang Zhang, Shugao Xie, Yan Zhou, Yinyin Xie, Ping Liu, Mingming Sun, Huasheng Xiao, Ying Jin, Xiaojian Sun, Zhu Chen, Qiuhua Huang, Saijuan Chen

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Setd2 is known as a histone-H3K36-specific methyltransferase. However, its role in physiological function remains unclear. In this study, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) toward primitive endoderm. Furthermore, we show that downregulated endoderm-related genes in Setd2-/- mESCs are associated with an aberrantly low level of Erk activity and that enforced expression of Fgfr3 can rescue the defective Erk pathway in Setd2-/- mESCs. Interestingly, the transcriptional initiation of Fgfr3 is directly regulated through histone H3K36me3 modification in its distal promoter region by Setd2. These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling.

Original languageEnglish (US)
Pages (from-to)1989-2002
Number of pages14
JournalCell Reports
Volume8
Issue number6
DOIs
StatePublished - Sep 25 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Zhang, Y., Xie, S., Zhou, Y., Xie, Y., Liu, P., Sun, M., Xiao, H., Jin, Y., Sun, X., Chen, Z., Huang, Q., & Chen, S. (2014). H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm. Cell Reports, 8(6), 1989-2002. https://doi.org/10.1016/j.celrep.2014.08.031