Nkx3-1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity

Kelly A. Holmes, Jun S. Song, Xiaole S. Liu, Myles Brown, Jason S. Carroll

Research output: Contribution to journalArticle

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 Nkxand 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 inbreast cancer.

Original languageEnglish (US)
Pages (from-to)7380-7385
Number of pages6
JournalCancer Research
Volume68
Issue number18
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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