Classical and Nonclassical Estrogen Receptor Action on Chromatin Templaces
Abstract
Improvement of hormone-based therapy in breast cancer and circumvention of its shortcomings is limited by the lack of detailed understanding of how steroids like estrogen work at a cellular and molecular level. The research supported by this award addressed the mechanism of action of estrogen action at its most fundamental level. Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression. specifically, experiments were proposed to assess the role of histone acetylation and high mobility group (HMG) chromatin proteins in estrogen receptor-directed transcription. Additionally, I sought to test whether in vitro transcription on chromatin templates could be used to address estrogen receptor action at nonclassical target genes The chief accomplishment of these studies addressed the role of chromatin modification in activator%dependent transcription of chromatin templates. We found that the chromatin assembly extracts provided a critical factor and that acetyl CoA could restore activator-dependent transcription, implicating a critical role for chromatin modification in transcriptional regulation. However, other data suggested that acetyl CoA may account for only part of the stimulatory activity. Further experiments to address these findings are in progress.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA405253
Entities
People
- Steve K. Nordeen
Organizations
- University of Colorado Health