Role of GCN5 in Estrogen Responses, Tumor Suppression, and Breast Development in Mice

摘要

Nucleosomes are folded together into chromatin structures that inhibit transcription. Studies here tested the idea that a histone acetyltransferase, Gcn5, that regulates chromatin folding is important for p53 functions and for estrogen responses. Experiments were 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 made progress towards all three aims. We examined Gcn5- dependence of estrogen responses in ER+ cell lines. We generated mice that carry null alleles for both Gcn5 and p53 in cis on chromosome 11. We generated mice that carry a conditional disruption allele for Gcn5 that will allow us to do a breast-specific knock out. Our studies will allow us to determine whether histone acetyltransferases provide targets for development of new drug therapies or diagnostic agents, furthering our advancement towards eradication of breast cancer.