Role of DNA Methylation in Modulating Transcription Factor Occupancy.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Maurano MT,Wang H,John S,Shafer A,Canfield T,Lee K,Stamatoyannopoulos JA

doi

10.1016/j.celrep.2015.07.024

subject

Has Abstract

pub_date

2015-08-18 00:00:00

pages

1184-95

issue

7

issn

2211-1247

pii

S2211-1247(15)00764-0

journal_volume

12

pub_type

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