title: Genome-wide DNA methylation analysis in cohesin mutant human cell lines.
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.
authors.affiliation: Division of Human Genetics, Abramson Research Institute, Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Jinglan
authors.initials: J
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Masashige
authors.initials: M
authors.lastname: Bando
authors.forename: Takehiko
authors.initials: T
authors.lastname: Itoh
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Li
authors.forename: Dinah
authors.initials: D
authors.lastname: Clark
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.forename: Kondo
authors.initials: K
authors.lastname: Tatsuro
authors.forename: Antonie D
authors.initials: AD
authors.lastname: Kline
authors.forename: Celia
authors.initials: C
authors.lastname: Chang
authors.forename: Hugo
authors.initials: H
authors.lastname: Vega
authors.forename: Laird G
authors.initials: LG
authors.lastname: Jackson
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D003635:De Lange Syndrome / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012091:Repetitive Sequences, Nucleic Acid; D012984:Software; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D006657:Histones; D000097722:Cohesins
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