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 language | English (US) |
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Pages (from-to) | 114-123 |
Number of pages | 10 |
Journal | STEM CELLS |
Volume | 34 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2016 |
Bibliographical note
Publisher Copyright:© AlphaMed Press.
Keywords
- Embryonic stem cells
- Neural differentiation
- RIP140
- Retinoic acid
- Transcription factors