Extracellular Matrix-Regulated Gene Expression RequiresCooperation 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 (ChIP) assays and mammary-specific genes as models, we show here that extracellular matrix (ECM) molecules and prolactin cooperate to induce histone acetylation and binding of transcription factors and the SWI/SNF complex to the {beta}- and ?-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both {beta}- and ?-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. ChIP 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. Coimmunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, C/EBP{beta}, and glucocorticoid receptor (GR). Thus, ECM- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of AdvancedScientific Computing Research. Office of Biological and EnvironmentalResearch; US Department of Defense. Breast Cancer Research ProgramDAMD17-01-1-0438 and DAMD17-01-01-0441 and W81XWH0410581, NationalInstitutes of Health Grant CA057621-13; Canadian Institute for HealthResearch
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 910587
- Report Number(s):
- LBNL-60669; JBCHA3; R&D Project: 443180; BnR: KP1104010; TRN: US200724%%260
- Journal Information:
- Journal of Biological Chemistry, Vol. 828, Issue 20; Related Information: Journal Publication Date: May 18, 2007; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- English
Similar Records
SWI/SNF chromatin remodeling complex is critical for the expression of microphthalmia-associated transcription factor in melanoma cells
Downregulation of SWI/SNF chromatin remodeling factor subunits modulates cisplatin cytotoxicity