Chromatin Regulation of EGFR Locus in Human Mammary Epithelial Cells
Annual summary rept. 1 May 2004-30 Apr 2005
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
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Relationship between chromatin remodeling and mammary tissue-specific gene transcription is not well understood. Using milk protein beta-casein as a marker, we investigate how extracellular matrix ECM and lactogenic hormone control transcription factors activity, and elucidate the role of histone acetylation and A P-dependent chromatin remodeling in the transcriptional regulation. By ChIP assays, we show that ECM cooperates with prolactin to induce binding of Stat5 and CEBPBeta in the Beta-casein promoter. We also show that the levels of acetylated histones increase in the Beta-casein promoter. However, increasing acetylated histone levels in the promoter region by TSA treatment failed to induce Beta-casein expression, suggesting histone acetylation is not sufficient for the gene transcription. Introduction of the ATPase-deficient SWISNF complex significantly blocked Beta-casein expression, indicating that ATP-dependent chromatin remodeling is required for the transcriptional activation of this gene. Taken together, these observations indicate that Beta-casein expression requires the concerted action of both transcription and chromatin remodeling factors.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research