Extracellular Matrix-regulated Gene Expression Requires Cooperation of SWI/SNF and Transcription Factors

• Published in: The Journal of biological chemistry Vol. 282; no. 20; pp. 14992 - 14999
• Main Authors: Xu, Ren, Spencer, Virginia A., Bissell, Mina J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.05.2007; American Society for Biochemistry and Molecular Biology
• Subjects: Acetylation; Adenosine Triphosphatases - metabolism; Animals; Caseins - biosynthesis; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cell Line; Chromatin Assembly and Disassembly - physiology; Chromatin Immunoprecipitation; Chromosomal Proteins, Non-Histone - metabolism; DNA Helicases - genetics; DNA Helicases - metabolism; Extracellular Matrix - metabolism; Female; Genes, Dominant - genetics; Histones - metabolism; Mammary Glands, Animal - cytology; Mammary Glands, Animal - metabolism; Mice; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Organ Specificity - physiology; Pregnancy; Prolactin - metabolism; Promoter Regions, Genetic - physiology; Protein Binding - physiology; Protein Processing, Post-Translational - physiology; Receptors, Glucocorticoid - metabolism; STAT5 Transcription Factor - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M610316200

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 β- and γ-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both β- and γ-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 β, 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.