Widespread plasticity in CTCF occupancy linked to DNA methylation
Open Access
- 5 September 2012
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 22 (9), 1680-1688
- https://doi.org/10.1101/gr.136101.111
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.Keywords
This publication has 69 references indexed in Scilit:
- The accessible chromatin landscape of the human genomeNature, 2012
- Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3Cell, 2011
- Human DNA methylomes at base resolution show widespread epigenomic differencesNature, 2009
- CCCTC-Binding Factor and the Transcription Factor T-bet Orchestrate T Helper 1 Cell-Specific Structure and Function at the Interferon-γ LocusImmunity, 2009
- Epigenetic Silencing of the p16INK4a Tumor Suppressor Is Associated with Loss of CTCF Binding and a Chromatin BoundaryMolecular Cell, 2009
- Histone modifications at human enhancers reflect global cell-type-specific gene expressionNature, 2009
- Design and analysis of ChIP-seq experiments for DNA-binding proteinsNature Biotechnology, 2008
- The LPS-Induced Transcriptional Upregulation of the Chicken Lysozyme Locus Involves CTCF Eviction and Noncoding RNA TranscriptionMolecular Cell, 2008
- Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human GenomeCell, 2007
- The Epigenomics of CancerCell, 2007