Widespread plasticity in CTCF occupancy linked to DNA methylation

By Hao Wang, Matthew T. Maurano, H. Qu, K. Varley, Jason Gertz, Florencia Pauli, Kristen Lee, T. Canfield, M. Weaver, R. Sandstrom and 4 more. Genome Research, 2012

599 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bde55b76aba686b27e1ee38c1ae7c76437b05ede

Citations in the corpus

• High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes (2014, unknown): “More recent work has identified CTCF primarily at unmethylated regions of the DNA [19,48].”
• Editing DNA methylation in the mammalian genome (2016, unknown): “Interestingly, methylation of the DNA recognition site of CTCF has been reported to block CTCF binding (Bell and Felsenfeld, 2000; Wang et al., 2012).”
• CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function (2015, unknown): “…Shen et al., 2012; Xie et al., 2007), and the genome-wide pattern of CTCF occupancy is cell-type specific (Kim et al., 2007; Shen et al., 2012; Wang et al., 2012); however, CBSs are enriched at constitutive boundaries of topologically associated domains (TADs) (Dixon et al., 2012; Gibcus and…”
• YY1 Is a Structural Regulator of Enhancer-Promoter Loops (2017, unknown): “…et al., 1993); Lin et al. (2010); Lobanenkov et al. (1990); Mendenhall et al. (2010); Moore et al. (2012); Natesan and Gilman (1993); Nora et al. (2016); Pope et al. (2014); Seto et al. (1991); Stadler et al. (2011); Wang et al. (2012); Wu et al. (2007); Xu et al. (2007); Yusufzai et al. (2004).”