Authors:
KA Holmes, JS Song, XS Liu, M Brown, JS Carroll
Journal name: 
Cancer Res
Citation info: 
68(18):7380-7385
Abstract: 
Estrogen receptor (ER)-associated cofactors and cooperating transcription factors are one of the primary components determining transcriptional activity of estrogen target genes and may constitute potential therapeutic targets. Recent mapping of ER-binding sites on a genome-wide scale has provided insight into novel cooperating factors based on the enrichment of transcription factor motifs within the ER-binding sites. We have used the ER-binding sites in combination with sequence conservation to identify the statistical enrichment of Nkx and LEF motifs. We find that Nkx3-1 and LEF-1 bind to several ER cis-regulatory elements in vivo, but they both function as transcriptional repressors of estrogen signaling. We show that Nkx3-1 and LEF-1 can inhibit ER binding to chromatin, suggesting competition for common chromatin-binding regions. These data provide insight into the role of Nkx3-1 and LEF-1 as potential regulators of the hormone response in breast cancer.
DOI: 
http://doi.org/10.1158/0008-5472.CAN-08-0133
Research group: 
Carroll Group
E-pub date: 
15 Sep 2008