Extracellular matrix-regulated gene expression requires cooperation of SWI/SNF and transcription factors.
Extracellular cues play crucial roles in the transcriptional regulation of tissue-specific genes, but whether and how these signals lead to chromatin remodeling is not understood and subject to debate. Using chromatin immunoprecipitation assays and mammary-specific genes as models, we show here that extracellular matrix molecules and prolactin cooperate to induce ... histone acetylation and binding of transcription factors and the SWI/SNF complex to the beta- and gamma-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both beta- and gamma-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. Chromatin immunoprecipitation analyses demonstrated that the ATPase activity of SWI/SNF is necessary for recruitment of RNA transcriptional machinery, but not for binding of transcription factors or for histone acetylation. Co-immunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, CCAAT/enhancer-binding protein beta, and glucocorticoid receptor. Thus, extracellular matrix- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.
Mesh Terms:
Acetylation, Adenosine Triphosphatases, Animals, CCAAT-Enhancer-Binding Protein-beta, Caseins, Cell Line, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, DNA Helicases, Extracellular Matrix, Female, Genes, Dominant, Histones, Mammary Glands, Animal, Mice, Mutation, Nuclear Proteins, Organ Specificity, Pregnancy, Prolactin, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Receptors, Glucocorticoid, STAT5 Transcription Factor, Transcription Factors, Transcription, Genetic
Acetylation, Adenosine Triphosphatases, Animals, CCAAT-Enhancer-Binding Protein-beta, Caseins, Cell Line, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, DNA Helicases, Extracellular Matrix, Female, Genes, Dominant, Histones, Mammary Glands, Animal, Mice, Mutation, Nuclear Proteins, Organ Specificity, Pregnancy, Prolactin, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Receptors, Glucocorticoid, STAT5 Transcription Factor, Transcription Factors, Transcription, Genetic
J. Biol. Chem.
Date: May. 18, 2007
PubMed ID: 17387179
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