Rinf Regulates Pluripotency Network Genes and Tet Enzymes in Embryonic Stem Cells

Mirunalini Ravichandran, Run Lei, Qin Tang, Yilin Zhao, Joun Lee, Liyang Ma, Stephanie Chrysanthou, Benjamin M. Lorton, Ales Cvekl, David Shechter, Deyou Zheng, Meelad M. Dawlaty

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The Retinoid inducible nuclear factor (Rinf), also known as CXXC5, is a nuclear protein, but its functions in the context of the chromatin are poorly defined. We find that in mouse embryonic stem cells (mESCs), Rinf binds to the chromatin and is enriched at promoters and enhancers of Tet1, Tet2, and pluripotency genes. The Rinf-bound regions show significant overlapping occupancy of pluripotency factors Nanog, Oct4, and Sox2, as well as Tet1 and Tet2. We found that Rinf forms a complex with Nanog, Oct4, Tet1, and Tet2 and facilitates their proper recruitment to regulatory regions of pluripotency and Tet genes in ESCs to positively regulate their transcription. Rinf deficiency in ESCs reduces expression of Rinf target genes, including several pluripotency factors and Tet enzymes, and causes aberrant differentiation. Together, our findings establish Rinf as a regulator of the pluripotency network genes and Tet enzymes in ESCs.

Original languageEnglish (US)
Pages (from-to)1993-2003.e5
JournalCell Reports
Volume28
Issue number8
DOIs
StatePublished - Aug 20 2019

Keywords

  • CXXC5
  • ESC
  • Nanog
  • Rinf
  • Tet enzymes
  • pluripotency

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ravichandran, M., Lei, R., Tang, Q., Zhao, Y., Lee, J., Ma, L., Chrysanthou, S., Lorton, B. M., Cvekl, A., Shechter, D., Zheng, D., & Dawlaty, M. M. (2019). Rinf Regulates Pluripotency Network Genes and Tet Enzymes in Embryonic Stem Cells. Cell Reports, 28(8), 1993-2003.e5. https://doi.org/10.1016/j.celrep.2019.07.080