Document Detail

The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene.
MedLine Citation:
PMID:  9271417     Owner:  NLM     Status:  MEDLINE    
Estrogen-related receptor alpha (ERR alpha) is an orphan member of the superfamily of nuclear hormone receptors. ERR alpha was initially isolated based on its sequence homology to the estrogen receptor but is not activated by classic estrogens. To identify possible physiologic functions for this orphan receptor, we cloned the mouse ERR alpha cDNA and used it to characterize the expression of ERR alpha transcripts and to identify potential ERR alpha target genes. RNA in situ hybridization studies detect ERR alpha transcripts in an organ-specific manner through mid- to late embryonic development, with persistent high-level expression in brown adipose tissue and intestinal mucosa. In the adult mouse, ERR alpha is most highly expressed in kidney, heart, and brown adipocytes, tissues which preferentially metabolize fatty acids. Binding site selection experiments show that ERR alpha preferentially binds to an ERR alpha response element (ERRE) containing a single consensus half-site, TNAAGGTCA. An ERRE is present in the 5'-flanking region of the gene encoding medium-chain acyl coenzyme A dehydrogenase (MCAD), a key enzyme involved in the mitochondrial beta-oxidation of fat. The MCAD nuclear receptor response element 1 (NRRE-1) interacts in vitro with ERR alpha expressed in COS-7 cells. Supershift experiments show that endogenous ERR alpha present in nuclear extracts obtained from a brown fat tumor cell line (HIB) interacts with NRRE-1. In the absence of its putative ligand, ERR alpha does not activate the MCAD promoter in transient transfection studies; however, a VP16-ERR alpha chimera activates natural and synthetic promoters containing NRRE-1. In addition, ERR alpha efficiently represses retinoic acid induction mediated by NRRE-1. These results demonstrate that ERR alpha can control the expression of MCAD through the NRRE-1 and thus may play an important role in regulating cellular energy balance in vivo.
R Sladek; J A Bader; V Giguère
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  17     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-09-22     Completed Date:  1997-09-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5400-9     Citation Subset:  IM    
Molecular Oncology Group, Royal Victoria Hospital, Montréal, Québec, Canada.
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MeSH Terms
Acyl-CoA Dehydrogenase
Adipocytes / cytology
Cell Differentiation
Cloning, Molecular
Fatty Acid Desaturases / genetics*
Gene Expression Regulation, Enzymologic*
Genes, Regulator
Hela Cells
Herpes Simplex Virus Protein Vmw65 / genetics
Promoter Regions, Genetic
Receptors, Cytoplasmic and Nuclear / metabolism*
Receptors, Estrogen / metabolism*
Recombinant Fusion Proteins / metabolism
Transcription, Genetic
Transcriptional Activation
Reg. No./Substance:
0/ERRalpha estrogen-related receptor; 0/Herpes Simplex Virus Protein Vmw65; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; EC 1.14.19.-/Fatty Acid Desaturases; EC Dehydrogenase

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