Journal article
Genome-wide DNA methylation analysis in cohesin mutant human cell lines
Nucleic acids research, v 38(17), pp 5657-5671
06 May 2010
PMID: 20448023
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The cohesin complex has recently been shown to be a key regulator of eukaryotic gene expression, although the mechanisms by which it exerts its effects are poorly understood. We have undertaken a genome-wide analysis of DNA methylation in cohesin-deficient cell lines from probands with Cornelia de Lange syndrome (CdLS). Heterozygous mutations in
NIPBL, SMC1A
and
SMC3
genes account for ∼65% of individuals with CdLS. SMC1A and SMC3 are subunits of the cohesin complex that controls sister chromatid cohesion, whereas NIPBL facilitates cohesin loading and unloading. We have examined the methylation status of 27 578 CpG dinucleotides in 72 CdLS and control samples. We have documented the DNA methylation pattern in human lymphoblastoid cell lines (LCLs) as well as identified specific differential DNA methylation in CdLS. Subgroups of CdLS probands and controls can be classified using selected CpG loci. The X chromosome was also found to have a unique DNA methylation pattern in CdLS. Cohesin preferentially binds to hypo-methylated DNA in control LCLs, whereas the differential DNA methylation alters cohesin binding in CdLS. Our results suggest that in addition to DNA methylation multiple mechanisms may be involved in transcriptional regulation in human cells and in the resultant gene misexpression in CdLS.
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Details
- Title
- Genome-wide DNA methylation analysis in cohesin mutant human cell lines
- Creators
- Jinglan Liu - Children's Hospital of PhiladelphiaZhe Zhang - University of PennsylvaniaMasashige Bando - Tokyo Institute of TechnologyTakehiko Itoh - Tokyo Institute of TechnologyMatthew A. Deardorff - University of PennsylvaniaJennifer R. Li - Drexel UniversityDinah Clark - Drexel UniversityManinder Kaur - Drexel UniversityKondo Tatsuro - Aichi Developmental Disability CenterAntonie D. Kline - Drexel UniversityCelia Chang - The Wistar InstituteHugo Vega - Icahn School of Medicine at Mount SinaiLaird G. Jackson - Drexel UniversityNancy B. Spinner - University of PennsylvaniaKatsuhiko Shirahige - Tokyo Institute of TechnologyIan D. Krantz - University of Pennsylvania
- Publication Details
- Nucleic acids research, v 38(17), pp 5657-5671
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000282173300011
- Scopus ID
- 2-s2.0-77957234402
- Other Identifier
- 991019350588504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology