Pooled ChIP-Seq Links Variation in Transcription Factor Binding to Complex Disease Risk.

ABSTRACT: Cis-regulatory elements such as transcription factor (TF) binding sites can be identified genome-wide, but it remains far more challenging to pinpoint genetic variants affecting TF binding. Here, we introduce a pooling-based approach to mapping quantitative trait loci (QTLs) for molecular-level traits. Applying this to five TFs and a histone modification, we mapped thousands of cis-acting QTLs, with over 25-fold lower cost compared to standard QTL mapping. We found that single genetic variants frequently affect binding of multiple TFs, and CTCF can recruit all five TFs to its binding sites. These QTLs often affect local chromatin and transcription but can also influence long-range chromosomal contacts, demonstrating a role for natural genetic variation in chromosomal architecture. Thousand

SUBMITTER: Tehranchi AK 

PROVIDER: S-EPMC4842172 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature