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

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

Research output: Contribution to journalArticle

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. In embryonic stem cells, pluripotency factors and Tet enzymes regulate gene expression and differentiation programs. Ravichandran et al. find that Rinf facilitates their recruitment to promoters and enhancers of stemness genes, including several pluripotency and Tet genes. Rinf positively regulates their transcription and ensures proper differentiation of embryonic stem cells.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Gene Regulatory Networks
Retinoids
Embryonic Stem Cells
Stem cells
Genes
Enzymes
Transcription
Chromatin
Stem Cell Factor
Nucleic Acid Regulatory Sequences
Nuclear Proteins
Gene expression
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rinf Regulates Pluripotency Network Genes and Tet Enzymes in Embryonic Stem Cells. / Ravichandran, Mirunalini; Lei, Run; Tang, Qin; Zhao, Y.; Lee, Joun; Ma, Liyang; Chrysanthou, Stephanie; Lorton, Benjamin M.; Cvekl, Ales; Shechter, David; Zheng, Deyou; Dawlaty, Meelad M.

In: Cell Reports, 01.01.2019.

Research output: Contribution to journalArticle

Ravichandran, Mirunalini ; Lei, Run ; Tang, Qin ; Zhao, Y. ; Lee, Joun ; Ma, Liyang ; Chrysanthou, Stephanie ; Lorton, Benjamin M. ; Cvekl, Ales ; Shechter, David ; Zheng, Deyou ; Dawlaty, Meelad M. / Rinf Regulates Pluripotency Network Genes and Tet Enzymes in Embryonic Stem Cells. In: Cell Reports. 2019.
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AU - Chrysanthou, Stephanie

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