Widespread plasticity in CTCF occupancy linked to DNA methylation
- Hao Wang1,5,
- Matthew T. Maurano1,5,
- Hongzhu Qu1,2,5,
- Katherine E. Varley3,
- Jason Gertz3,
- Florencia Pauli3,
- Kristen Lee1,
- Theresa Canfield1,
- Molly Weaver1,
- Richard Sandstrom1,
- Robert E. Thurman1,
- Rajinder Kaul1,
- Richard M. Myers3 and
- John A. Stamatoyannopoulos1,4,6
- 1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
- 2Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China;
- 3HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA;
- 4Department of Medicine, University of Washington, Seattle, Washington 98195, USA
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↵5 These authors contributed equally to this work.
Abstract
CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have long been assumed to be largely invariant across different cellular environments. Here we analyze genome-wide occupancy patterns of CTCF by ChIP-seq in 19 diverse human cell types, including normal primary cells and immortal lines. We observed highly reproducible yet surprisingly plastic genomic binding landscapes, indicative of strong cell-selective regulation of CTCF occupancy. Comparison with massively parallel bisulfite sequencing data indicates that 41% of variable CTCF binding is linked to differential DNA methylation, concentrated at two critical positions within the CTCF recognition sequence. Unexpectedly, CTCF binding patterns were markedly different in normal versus immortal cells, with the latter showing widespread disruption of CTCF binding associated with increased methylation. Strikingly, this disruption is accompanied by up-regulation of CTCF expression, with the result that both normal and immortal cells maintain the same average number of CTCF occupancy sites genome-wide. These results reveal a tight linkage between DNA methylation and the global occupancy patterns of a major sequence-specific regulatory factor.
Footnotes
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↵6 Corresponding author
E-mail jstam{at}uw.edu
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[Supplemental material is available for this article.]
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Article and supplemental material are at http://www.genome.org/cgi/doi/10.1101/gr.136101.111.
Freely available online through the Genome Research Open Access option.
- Received December 9, 2011.
- Accepted April 30, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
