Open AccessRetinoic Acid Induces Ubiquitination‐Resistant RIP140/LSD1 Complex to Fine‐Tune P ax6 Gene in Neuronal Differentiation
Author(s) -
Wu ChengYing,
Persaud Shawna D.,
Wei LiNa
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2190
Subject(s) - biology , retinoic acid , demethylase , microbiology and biotechnology , cellular differentiation , nuclear receptor , histone , gene , biochemistry , transcription factor
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. S tem C ells 2016;34:114–123