Role of GCN5 in Estrogen Response, Tumor Suppression, and Breast Development in Mice
Abstract
DNA is tightly packed into the eukaryotic nucleus in the form of chromatin. Chromatin is built of nucleosomal repeat units comprised of histone proteins and DNA. Nucleosomes are folded together into higher order structures that inhibit transcription. This proposal tests the idea that an enzyme that regulates chromatin folding through post-translational modification of the histones is important for p53 functions and for estrogen responses, as well as for normal breast development. Experiments are proposed to: (1) determine whether Gcn5 serves as a coactivator for activation of gene expression by the estrogen receptor; (2) examine biochemical, molecular, and genetic connections between Gcn5 and p53 and (3) to generate a mammary gland specific knock out' of Gcn5 in mice to create a mouse model for Gcn5 functions in breast development and tumor formation. We have made progress towards all three aims. We have created cell lines carrying stable reporter genes carrying estrogen response elements assembled into chromatin. We have uncovered biochemical and genetic connections between Gcn5 and p53. We have generated a conditional disruption allele for Gcn5. Together these studies should provide important new information about breast cancer biology. Moreover, histone acetyltransferases may also provide novel targets in the future for development of new drug therapies or diagnostic agents, furthering our advancement towards eradication of this disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA395509
Entities
People
- Sharon Y. Roth Dent
Organizations
- The University of Texas MD Anderson Cancer Center