Interactions between CCAAT enhancer binding protein δ and estrogen receptor α control insulin-like growth factor I (igf1) and estrogen receptor-dependent gene expression in osteoblasts
| Autor: | Thomas L. McCarthy, Michael Centrella, Weizhong Chang, Macarena Parra |
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| Rok vydání: | 2005 |
| Předmět: |
CCAAT-Enhancer-Binding Protein-delta
medicine.medical_treatment Estrogen receptor Biology Rats Sprague-Dawley Insulin-like growth factor Gene expression Genetics medicine Animals Insulin-Like Growth Factor I Promoter Regions Genetic Protein kinase A Transcription factor Cells Cultured Regulation of gene expression Osteoblasts Estradiol Ccaat-enhancer-binding proteins Estrogen Receptor alpha General Medicine Cyclic AMP-Dependent Protein Kinases Molecular biology Rats Gene Expression Regulation Receptors Estrogen CCAAT-Enhancer-Binding Proteins Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Transcription Factors |
| Zdroj: | Gene. 345:225-235 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2004.11.017 |
| Popis: | Although ambient levels of estradiol and synthesis of the osteoblast growth factor IGF-I are inversely related in vivo, estradiol has little or no direct effect on igf1 gene expression in rat osteoblasts in vitro. Rather, estradiol suppresses the effect of hormones that enhance igf1 expression through protein kinase A dependent activation of CCAAT enhancer binding protein (C/EBP) transcription factors. We show here that inhibition of C/EBP activity by estradiol relates to the level of estrogen receptor alpha (ERalpha) expression, and that a complex between hormone-activated ERalpha and C/EBPdelta inhibits transcription by each factor. Protein fragmentation, co-immunoprecipitation, and gene expression studies identified domains for physical and functional interactions between ERalpha and C/EBPdelta. Whereas ERalpha and fragments comprising its various domains associated with C/EBPdelta, only ERalpha fragment A/B alone replicated the suppressive effect of intact ERalpha on endogenous C/EBPdelta activity. Complementary studies showed that several carboxyl regions of C/EBPdelta cooperatively inhibit ERalpha dependent transcription. Therefore, multiple domains of C/EBPdelta and ERalpha can physically interact to alter gene expression in osteoblasts in selective ways that depend on variations in the local hormone environment. Their combined effects on one important gene target, igf1, may help to determine the balance in the overall rates of bone formation. |
| Databáze: | OpenAIRE |
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