Widespread plasticity in CTCF occupancy linked to DNA methylation.

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.

journal_name

Genome Res

journal_title

Genome research

authors

Wang H,Maurano MT,Qu H,Varley KE,Gertz J,Pauli F,Lee K,Canfield T,Weaver M,Sandstrom R,Thurman RE,Kaul R,Myers RM,Stamatoyannopoulos JA

doi

10.1101/gr.136101.111

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

1680-8

issue

9

eissn

1088-9051

issn

1549-5469

pii

22/9/1680

journal_volume

22

pub_type

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