In Vivo and In Vitro Analysis of the Regulation of c-myc Proto-Oncogene Expression in Human Breast Cancer.
Annual rept. 15 Sep 94-14 Sep 95,
MASSACHUSETTS GENERAL HOSPITAL BOSTON
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The purpose of this research is to characterize the factors controlling the expression of c-myc and other genes that are commonly mis-regulated in transformed cells, Genomic DNA exists in the form of chromatin, which generally renders the DNA inaccessible to factors that promote gene expression. Here we report characterization of a cellular protein complex, hSW1SNF, that can alter chromatin structure and facilitate the interaction of transcription factors with chromatin. The results indicate that the change in chromatin structure induced by hSW1SNF is stable and not transient in nature, that hSW1SNF activity requires ATP hydrolysis, that the hydrolysis of ATP is likely utilized to alter the chromatin structure as opposed to modifying or altering the conformation of hSW1SNF, and that the increased ability of transcription factors to bind to chromatin is not dependent on concurrent hSW1SNF activity, which indicates that hS1SNF facilitated binding of transcription factors to nucleosomal DNA is a multi-step process. The results also show that hSWISNF can increase transcriptional elongation in vitro on a reconstituted nucleosomal human hsp7O promoter, a promoter that, like c-myc, is regulated at the level of transcription initiation and transcription elongation.
- Anatomy and Physiology