title: 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.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Maurano
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Qu
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Varley
authors.forename: Jason
authors.initials: J
authors.lastname: Gertz
authors.forename: Florencia
authors.initials: F
authors.lastname: Pauli
authors.forename: Kristen
authors.initials: K
authors.lastname: Lee
authors.forename: Theresa
authors.initials: T
authors.lastname: Canfield
authors.forename: Molly
authors.initials: M
authors.lastname: Weaver
authors.forename: Richard
authors.initials: R
authors.lastname: Sandstrom
authors.forename: Robert E
authors.initials: RE
authors.lastname: Thurman
authors.forename: Rajinder
authors.initials: R
authors.lastname: Kaul
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins