Nuclear Receptors in Gene Regulation

We are trying to understand the role of nuclear receptors in gene regulation by studying their binding sites across the genome as well as the gene expression changes they produce.  We are currently focused on type I nuclear receptors such as estrogen receptor as well as type II nuclear receptors that are known to heterodimerize with RXR.

Estrogen Receptor alpha

 We are looking into ligand specificity to gain insight into how estrogen receptor responds to different chemicals. By using ChIP-seq on cell lines that have either been treated with genistein, bisphenol A, or a native estrogen, we can determine to which genomic locations estrogen receptor binds when exposed to each ligand and try to determine why.

            We are also studying cell type specificity to learn about estrogen receptor binding site selection.  We are mapping estrogen receptor binding in breast cancer cell lines (including both a luminal and basal form) as well as an endometrial cancer cell line in order to determine where on the genome the receptor binds in each cell type.  To understand cell type specificity, we are examining the association between ER binding and DNA methylation as well as chromatin accessibility.

 

Related Publications

Simpson, N. E., Gertz, J., Imberg, K., Myers, R. M. and Garabedian, M. J.  (2011).  Enhanced genome-wide occupancy of estrogen receptor alpha by the co-chaperone p23 in breast cancer cells.  Molec. Endocrin.  Nov 10.  [Epub ahead of print].  PMID: 22074947.  [PMC Journal - In Process]. PDF

Reddy, T. E., Pauli, F., Sprouse, R. O., Neff, N. F., Newberry, K. M., Garabedian, M. J. and Myers, R. M.  (2009). Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation.  Genome Res. 19: 2163-2171.  PMID: 19801529.  PMCID: PMC2792167. PDF