Mapping ER? genomic binding sites reveals unique genomic features and identifies EBF1 as an ER? interactor.

ABSTRACT: Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ER? and ER?. However, many of the targets for ER? in cell physiology remain elusive. Here, the C4-12/Flag.ER? cell line which stably expressed Flag.ER? is used to study ER? genomic functions without ER? interference. Mapping ER? binding sites in these cells reveals ER? unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ER? target genes. Gene ontology analysis reveals that ER? targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ER? binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ER? binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ER? binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ER? genomic functions in our cell model, we confirm the anti-proliferative role of ER? and discover the novel cross talk of ER? with EBF1 which has various implications in normal physiology.

SUBMITTER: Le TP 

PROVIDER: S-EPMC3738513 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature