RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis.
RIP140 is a corepressor for nuclear receptors that regulates energy expenditure in adipose tissue by suppressing the expression of clusters of metabolic genes involved in glucose and lipid metabolism. The gene encoding RIP140/Nrip1 contains only one coding exon but has multiple promoters and 5' non-coding exons that are subject to alternative splicing. In adipocytes we have defined a promoter, referred to as P2, that is preferentially utilized and activated during adipogenesis. Expression studies and chromatin immunoprecipitation experiments indicate that estrogen-related receptor alpha (ERRalpha), the level of which increases during adipogenesis in parallel with RIP140, stimulates transcription from the P2 promoter. Further analysis indicates that ERRalpha is capable of activating RIP140 gene transcription by two mechanisms, directly by binding to an estrogen receptor element/ERR element at -650/-633 and indirectly through Sp1 binding sites in the proximal promoter. Thus, the up-regulation of RIP140 by ERRalpha during adipogenesis may provide an inhibitory feedback mechanism to control the expression of many nuclear receptor target genes.
Nichol
Donna
D
Institute of Reproductive and Developmental Biology, Imperial College London, Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom.
Christian
Mark
M
Steel
Jennifer H
JH
White
Roger
R
Parker
Malcolm G
MG
D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D047628:Estrogen Receptor alpha; C000627127:NRIP1 protein, human; C000627128:Nrip1 protein, mouse; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1