title: Retinoic Acid Induces Ubiquitination-Resistant RIP140/LSD1 Complex to Fine-Tune Pax6 Gene in Neuronal Differentiation.
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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Shawna D
authors.initials: SD
authors.lastname: Persaud
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D056466:Histone Demethylases / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D000071841:PAX6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D054875:Ubiquitination / Q000187:drug effects*
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D056971:Nuclear Receptor Co-Repressor 1; D000071841:PAX6 Transcription Factor; D014212:Tretinoin; D056466:Histone Demethylases; C504076:KDM1a protein, mouse
keywords: Embryonic stem cells; Neural differentiation; RIP140; Retinoic acid; Transcription factors