Profiles of Growth Hormone (Gh)-regulated Genes Reveal Time-dependent Responses and Identify a Mechanism for Regulation of Activating Transcription Factor 3 by Gh.
From: Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, 48109, USA.
The Journal of biological chemistry
- Publish Date: Feb 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 7
- Pages: 4132-41
- Medium: Print
- Language: English
- Citation (JAMA): Huo Jeffrey S, McEachin Richard C, Cui Tracy Xiao, et al. Profiles of Growth Hormone (Gh)-regulated Genes Reveal Time-dependent Responses and Identify a Mechanism for Regulation of Activating Transcription Factor 3 by Gh.. J. Biol. Chem. Feb 2006;281:4132-41
Abstract
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.
Mesh Headings (Keywords): 3T3 Cells, Activating Transcription Factor 3, Adipocytes, Animals, CCAAT-Enhancer-Binding Protein-beta, Cholesterol, Fatty Acids, Gene Expression Regulation, Growth Hormone, Mice, Promoter Regions (Genetics), Time Factors, Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 16326703
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