Journal
GENOME RESEARCH
Volume 23, Issue 10, Pages 1624-1635Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.150136.112
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Funding
- Wellcome Trust [084358/Z/07/Z]
- Philip Harris prize studentship fund
- British Heart Foundation studentship [FS/08/051/25748]
- MRC
- BBSRC Doctoral Training Grant
- RCUK fellowship program
- King's College London
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award
- King's College London and King's College Hospital NHS Foundation Trust
- Biotechnology and Biological Sciences Research Council [1108059] Funding Source: researchfish
- British Heart Foundation [PG/13/35/30236] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [836374] Funding Source: researchfish
- Medical Research Council [G1001689] Funding Source: researchfish
- MRC [G1001689] Funding Source: UKRI
- Wellcome Trust [084358/Z/07/Z] Funding Source: Wellcome Trust
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DNA binding factors are essential for regulating gene expression. CTCF and cohesin are DNA binding factors with central roles in chromatin organization and gene expression. We determined the sites of CTCF and cohesin binding to DNA in mouse brain, genome wide and in an allele-specific manner with high read-depth ChIP-seq. By comparing our results with existing data for mouse liver and embryonic stem (ES) cells, we investigated the tissue specificity of CTCF binding sites. ES cells have fewer unique CTCF binding sites occupied than liver and brain, consistent with a ground-state pattern of CTCF binding that is elaborated during differentiation. CTCF binding sites without the canonical consensus motif were highly tissue specific. In brain, a third of CTCF and cohesin binding sites coincide, consistent with the potential for many interactions between cohesin and CTCF but also many instances of independent action. In the context of genomic imprinting, CTCF and/or cohesin bind to a majority but not all differentially methylated regions, with preferential binding to the unmethylated parental allele. Whether the parental allele-specific methylation was established in the parental germlines or post-fertilization in the embryo is not a determinant in CTCF or cohesin binding. These findings link CTCF and cohesin with the control regions of a subset of imprinted genes, supporting the notion that imprinting control is mechanistically diverse.
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