Identification of Estrogen Receptor Beta Binding Sites in the Human Genomes
Abstract
ER knock-out mice developed prostatic hyperplasia at late age, suggesting an important role of ER in the development of the prostate as well as prostate cancer. Here we describe a study that thoroughly investigates the genomic function of ER . A FLAG-tagged ER was stably expressed in MCF7 C4-12 cells, which allowed ER transcriptional activity to be studied in an ER -independent background. Interestingly, in our chromatin immunoprecipitation followed by sequencing (ChIP-seq) analyses, looking at ER global binding sites, while the most prevalent binding motif was the canonical ERE, ~30% of ER binding regions also carried the binding motif of EBF1 (Early B-cell Factor 1). Further investigations revealed EBF1 downregulated ER protein stability and transcriptional activity via a direct interaction. These results, at least to our knowledge, are the first to indicate crosstalk between EBF and ER activities on a large scale. Moreover, in conjunction with global run-on followed by sequencing (GRO-seq), looking at nascent RNA generated at the time of ER binding events, still to be completed, our results should reveal a global picture of how ER regulates its direct target genes, as well as the role of EBF proteins in this process.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA549088
Entities
People
- Thien Le
Organizations
- University of Chicago