Widespread site-dependent buffering of human regulatory polymorphism.

ABSTRACT: The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we comprehensively analyzed heritable genome-wide binding patterns of a major sequence-specific regulator (CTCF) in relation to genetic variability in binding site sequences across a multi-generational pedigree. We localized and quantified CTCF occupancy by ChIP-seq in 12 related and unrelated individuals spanning three generations, followed by comprehensive targeted resequencing of the entire CTCF-binding landscape across all individuals. We identified hundreds of variants with

SUBMITTER: Maurano MT 

PROVIDER: S-EPMC3310774 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature