title: 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.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: matthew.maurano@nyumc.org.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Maurano
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: John
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Shafer
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Canfield
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D006801:Humans; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D014157:Transcription Factors