A β-catenin/TCF-coordinated chromatin loop at MYC integrates 5′ and 3′ Wnt responsive enhancers

Gregory S. Yochum, Colette M. Sherrick, Mary MacPartlin, Richard H. Goodman

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Aberrant MYC gene expression by the Wnt/β-catenin pathway is implicated in colorectal carcinogenesis. Wnt/β-catenin signaling stimulates association of the β-catenin coactivator complex with two Wnt responsive enhancers (WREs) located in close proximity to MYC gene boundaries. Each enhancer directly binds members of the TCF/Lef family of transcription factors that, in turn, recruit β-catenin. In a previous report, we showed that the downstream MYC enhancer (MYC 3′ WRE) cooperated with the upstream enhancer (MYC 5′ WRE) to activate expression of a heterologous reporter gene in response to Wnt/β-catenin and mitogen signaling. Here we use chromatin conformation capture (3C) to show that the MYC 5′ and 3′ WREs are juxtaposed at the genomic MYC locus during active transcription. This MYC 5′3′ chromatin loop is present in HCT116 human colorectal cancer cells that contain high levels of nuclear β-catenin and is absent in HEK293 cells that contain trace amounts of nuclear β-catenin. Depletion of functional β-catenin/TCF complexes blocks formation of the MYC 5′3 chromatin loop. Furthermore, we find that the chromatin loop is absent in quiescent cells, but is rapidly and transiently induced by serum mitogens in a β-catenin-dependent manner. Thus,wepropose that a distinct chromatin architecture coordinated by β-catenin/TCF-bound WREs accompanies transcriptional activation of MYC gene expression.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Chromatin conformation capture
  • Colon cancer

ASJC Scopus subject areas

  • General

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