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  • Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

PLoS genetics (2014-11-21)
Zhihao Ding, Yunyun Ni, Sander W Timmer, Bum-Kyu Lee, Anna Battenhouse, Sandra Louzada, Fengtang Yang, Ian Dunham, Gregory E Crawford, Jason D Lieb, Richard Durbin, Vishwanath R Iyer, Ewan Birney
ABSTRACT

Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes. In order to identify quantitative trait loci (QTLs) that influence the binding of a transcription factor in humans, we measured binding of the multifunctional transcription and chromatin factor CTCF in 51 HapMap cell lines. We identified thousands of QTLs in which genotype differences were associated with differences in CTCF binding strength, hundreds of them confirmed by directly observable allele-specific binding bias. The majority of QTLs were either within 1 kb of the CTCF binding motif, or in linkage disequilibrium with a variant within 1 kb of the motif. On the X chromosome we observed three classes of binding sites: a minority class bound only to the active copy of the X chromosome, the majority class bound to both the active and inactive X, and a small set of female-specific CTCF sites associated with two non-coding RNA genes. In sum, our data reveal extensive genetic effects on CTCF binding, both direct and indirect, and identify a diversity of patterns of CTCF binding on the X chromosome.

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