Document Detail

Profiles of growth hormone (GH)-regulated genes reveal time-dependent responses and identify a mechanism for regulation of activating transcription factor 3 by GH.
MedLine Citation:
PMID:  16326703     Owner:  NLM     Status:  MEDLINE    
In examination of mechanisms regulating metabolic responses to growth hormone (GH), microarray analysis identified 561 probe sets showing time-dependent patterns of expression in GH-treated 3T3-F442A adipocytes. Biological functions significantly over-represented among GH-regulated genes include regulators of transcription at early times, and lipid biosynthesis, cholesterol biosynthesis, and mediators of immune responses at later times (48 h). One novel GH-induced gene encodes activating transcription factor 3 (ATF3). Atf3 mRNA expression and promoter activity were stimulated by GH. Genes for ATF3 and growth arrest and DNA damage-inducible gene 45 gamma (GADD45gamma) showed similar time-dependent patterns of responses to GH, suggesting similar regulatory mechanisms. A conserved sequence in the promoters of the Atf3 and Gadd45gamma genes contains a CCAAT/enhancer-binding protein (C/EBP) site previously observed in the Gadd45gamma promoter, suggesting a novel corresponding C/EBP site in the Atf3 promoter. C/EBPbeta was found to bind to the predicted Atf3 C/EBP site, and C/EBPbeta enhanced the activation of the wild-type Atf3 promoter. Mutation of the predicted Atf3 C/EBP site disrupted Atf3 promoter activation not only by C/EBPbeta but also by GH. These findings suggest that GH regulates transcription of Atf3 through a mechanism utilizing factors, such as C/EBPbeta, which bind to a novel C/EBP site.
Jeffrey S Huo; Richard C McEachin; Tracy Xiao Cui; Nisha K Duggal; Tsonwin Hai; David J States; Jessica Schwartz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2005-12-01
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-13     Completed Date:  2006-03-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4132-41     Citation Subset:  IM    
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, 48109, USA.
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MeSH Terms
3T3 Cells
Activating Transcription Factor 3 / genetics*
Adipocytes / metabolism
CCAAT-Enhancer-Binding Protein-beta / physiology
Cholesterol / biosynthesis
Fatty Acids / biosynthesis
Gene Expression Regulation / drug effects*
Growth Hormone / pharmacology*
Promoter Regions, Genetic
Time Factors
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Activating Transcription Factor 3; 0/Atf3 protein, mouse; 0/CCAAT-Enhancer-Binding Protein-beta; 0/Fatty Acids; 57-88-5/Cholesterol; 9002-72-6/Growth Hormone

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