Three-dimensional analysis reveals altered chromatin interaction by enhancer inhibitors harbors TCF7L2-regulated cancer gene signature.

Distal regulatory elements influence the activity of gene promoters through chromatin looping. Chromosome conformation capture (3C) methods permit identification of chromatin contacts across different regions of the genome. However, due to limitations in the resolution of these methods, the detection of functional chromatin interactions remains a challenge.

Altering cancer transcriptomes using epigenomic inhibitors.

Background: Due to the hyper-activation of WNT signaling in a variety of cancer types, there has been a strong drive to develop pathway-specific inhibitors with the eventual goal of providing a chemotherapeutic antagonist of WNT signaling to cancer patients. A new category of drugs, called epigenetic inhibitors, are being developed that hold high promise for inhibition of the WNT pathway. The canonical WNT signaling pathway initiates when WNT ligands bind to receptors, causing the nuclear localization of the co-activator β-catenin (CTNNB1), which leads to an association of β-catenin with a member of the TCF transcription factor family at regulatory regions of WNT-responsive genes.

Comprehensive functional annotation of 77 prostate cancer risk loci.

Genome-wide association studies (GWAS) have revolutionized the field of cancer genetics, but the causal links between increased genetic risk and onset/progression of disease processes remain to be identified. Here we report the first step in such an endeavor for prostate cancer. We provide a comprehensive annotation of the 77 known risk loci, based upon highly correlated variants in biologically relevant chromatin annotations--we identified 727 such potentially functional SNPs.

Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3.

Background: The TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in six human cell lines.