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Cell Rep. 2015 Aug 18;12(7):1184-95. doi: 10.1016/j.celrep.2015.07.024. Epub 2015 Aug 6.

Role of DNA Methylation in Modulating Transcription Factor Occupancy.

Author information

1
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: matthew.maurano@nyumc.org.
2
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
3
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: jstam@uw.edu.

Abstract

Although DNA methylation is commonly invoked as a mechanism for transcriptional repression, the extent to which it actively silences transcription factor (TF) occupancy sites in vivo is unknown. To study the role of DNA methylation in the active modulation of TF binding, we quantified the effect of DNA methylation depletion on the genomic occupancy patterns of CTCF, an abundant TF with known methylation sensitivity that is capable of autonomous binding to its target sites in chromatin. Here, we show that the vast majority (>98.5%) of the tens of thousands of unoccupied, methylated CTCF recognition sequences remain unbound upon abrogation of DNA methylation. The small fraction of sites that show methylation-dependent binding in vivo are in turn characterized by highly variable CTCF occupancy across cell types. Our results suggest that DNA methylation is not a primary groundskeeper of genomic TF landscapes, but rather a specialized mechanism for stabilizing intrinsically labile sites.

PMID:
26257180
DOI:
10.1016/j.celrep.2015.07.024
[Indexed for MEDLINE]
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