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 Resjournal_title
Genome researchauthors
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 JAdoi
10.1101/gr.136101.111subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1680-8issue
9eissn
1088-9051issn
1549-5469pii
22/9/1680journal_volume
22pub_type
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