Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in VDR transactivation during keratinocyte differentiation.
Cell programs such as proliferation and differentiation involve the sequential activation and repression of gene expression. Vitamin D, via its active metabolite 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)), controls the proliferation and differentiation of a number of cell types, including keratinocytes, by directly regulating transcription. Two classes of coactivators, the Vitamin D receptor (VDR) interacting proteins (DRIP/mediator) and the p160 steroid receptor coactivator family (SRC/p160), control the actions of nuclear hormone receptors, including the Vitamin D receptor. However, the relationship between these two classes of coactivators is not clear. Using GST-VDR affinity beads, we have identified the DRIP/mediator complex as the major VDR binding complex in proliferating keratinocytes. After the cells differentiated, members of the SRC/p160 family were identified in the complex but not major DRIP subunits. Both DRIP205 and SRC-3 potentiated Vitamin D-induced transcription in proliferating cells, but during differentiation, DRIP205 was no longer effective. These results indicate that these two distinct coactivators are differentially involved in Vitamin D regulation of gene transcription during keratinocyte differentiation, suggesting that these coactivators are part of the means by which the temporal sequence of gene expression is regulated during the differentiation process.
Oda
Yuko
Y
Department of Medicine, University of California San Francisco, Veterans Affairs Medical Center San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA. y2073@itsa.ucsf.edu
Sihlbom
Carina
C
Chalkley
Robert J
RJ
Huang
Lan
L
Rachez
Christophe
C
Chang
Chao-Pei Betty
CP
Burlingame
Alma L
AL
Freedman
Leonard P
LP
Bikle
Daniel D
DD
D000818:Animals; D002454:Cell Differentiation; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D056892:Mediator Complex; D009687:Nuclear Proteins / Q000502:physiology*; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
C113182:DRIP, VDR interacting protein complex; D056892:Mediator Complex; D009687:Nuclear Proteins; D018167:Receptors, Calcitriol; C470693:Sra1 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors