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


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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Publication Info

Ding, Zhihao, Yunyun Ni, Sander W Timmer, Bum-Kyu Lee, Anna Battenhouse, Sandra Louzada, Fengtang Yang, Ian Dunham, et al. (2014). Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association. PLoS Genet, 10(11). p. e1004798. 10.1371/journal.pgen.1004798 Retrieved from https://hdl.handle.net/10161/10680.

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Gregory E. Crawford

Professor in Pediatrics

My primary research interest is understanding how the genome is regulated.  The human genome contains approximately 25,000 genes, which are encoded in ~2% of the genome. The overarching goal of my research program is to identify and characterize how these genes are turned on and off in different cell types, tissues, development states, environmental responses, diseases, and individuals. By understanding where all gene regulatory elements are located, how they work to regulate gene expression, and how non-coding variants within these regions affect function, my research program can address a number of important basic and clinical questions.

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