Characterization of the transcriptional machinery bound across the widely presumed type 2 diabetes causal variant, rs7903146, within TCF7L2.

ABSTRACT: Resolving the underlying functional mechanism to a given genetic association has proven extremely challenging. However, the strongest associated type 2 diabetes (T2D) locus reported to date, TCF7L2, presents an opportunity for translational analyses, as many studies in multiple ethnicities strongly point to SNP rs7903146 in intron 3 as being the causal variant within this gene. We carried out oligo pull-down combined with mass spectrophotometry (MS) to elucidate the specific transcriptional machinery across this SNP using protein extracts from HCT116 cells. We observed that poly (ADP-ribose) polymerase 1 (PARP-1) is by far the most abundant binding factor. Pursuing the possibility of a feedback mechanism, we observed that PARP-1, along with the next most abundant binding proteins, DNA topo

SUBMITTER: Xia Q 

PROVIDER: S-EPMC4266734 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature