Retinoic Acid Induces Ubiquitination-Resistant RIP140/LSD1 Complex to Fine-Tune Pax6 Gene in Neuronal Differentiation

Cheng-Ying Wu, Shawna D. Persaud, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Receptor-interacting protein 140 (RIP140) is a wide-spectrum coregulator for hormonal regulation of gene expression, but its activity in development/stem cell differentiation is unknown. Here, we identify RIP140 as an immediate retinoic acid (RA)-induced dual-function chaperone for LSD1 (lysine-specific demethylase 1). RIP140 protects LSD1's catalytic domain and antagonizes its Jade-2-mediated ubiquitination and degradation. In RA-induced neuronal differentiation, the increased RIP140/LSD1 complex is recruited by RA-elevated Pit-1 to specifically reduce H3K4me2 modification on the Pax6 promoter, thereby repressing RA-induction of Pax6. This study reveals a new RA-induced gene repressive mechanism that modulates the abundance, enzyme quality, and recruitment of histone modifier LSD1 to neuronal regulator Pax6, which provides a homeostatic control for RA induction of neuronal differentiation.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalSTEM CELLS
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2016

Bibliographical note

Publisher Copyright:
© AlphaMed Press.

Keywords

  • Embryonic stem cells
  • Neural differentiation
  • RIP140
  • Retinoic acid
  • Transcription factors

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