A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers.

ABSTRACT: Aberrant MYC gene expression by the Wnt/beta-catenin pathway is implicated in colorectal carcinogenesis. Wnt/beta-catenin signaling stimulates association of the beta-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 beta-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/beta-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.

SUBMITTER: Yochum GS 

PROVIDER: S-EPMC2806753 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature