Genome-wide DNA methylation analysis in cohesin mutant human cell lines.
Genome-wide DNA methylation analysis in cohesin mutant human cell lines.
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DOI：
10.1093/nar/gkq346
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发表时间：
2010-09
影响因子：
14.9
通讯作者：
Krantz ID
中科院分区：
文献类型：
--
作者：
Liu J;Zhang Z;Bando M;Itoh T;Deardorff MA;Li JR;Clark D;Kaur M;Tatsuro K;Kline AD;Chang C;Vega H;Jackson LG;Spinner NB;Shirahige K;Krantz ID
最近的研究表明，粘附素复合物是真核基因表达的关键调节因子，但其发挥作用的机制还不清楚。我们对来自科尔内利亚德兰格综合征（CdLS）先证者的粘连蛋白缺陷细胞系进行了全基因组DNA甲基化分析。NIPBL、SMC1A和SMC3基因的杂合突变占CdLS患者的约65%。SMC 1A和SMC 3是控制姐妹染色单体凝聚力的凝聚素复合物的亚基，而NIPBL促进凝聚素加载和卸载。我们检测了72个CdLS和对照样品中27578个CpG二核苷酸的甲基化状态。我们已经记录了人类淋巴母细胞系（LCL）中的DNA甲基化模式，并在CdLS中鉴定了特异性差异DNA甲基化。CdLS先证者和对照的亚组可以使用选择的CpG基因座进行分类。在CdLS中还发现X染色体具有独特的DNA甲基化模式。在对照LCL中，粘附素优先与低甲基化DNA结合，而在CdLS中，差异DNA甲基化改变粘附素结合。我们的研究结果表明，除了DNA甲基化的多种机制可能参与在人类细胞中的转录调控，并在由此产生的基因在CdLS的错误表达。
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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影响因子：
7
作者：
Cheung, Vivian G.;Ewens, Warren J.
通讯作者：
Ewens, Warren J.
影响因子：
9.8
作者：
Deardorff, Matthew A.;Kaur, Maninder;Krantz, Ian D.
通讯作者：
Krantz, Ian D.
影响因子：
64.8
作者：
Hadjur, Suzana;Williams, Luke M.;Ryan, Natalie K.;Cobb, Bradley S.;Sexton, Tom;Fraser, Peter;Fisher, Amanda G.;Merkenschlager, Matthias
通讯作者：
Merkenschlager, Matthias
影响因子：
7
作者：
Bibikova, Marina;Chudin, Eugene;Fan, Jian-Bing
通讯作者：
Fan, Jian-Bing
影响因子：
30.8
作者：
Kanno, Tatsuo;Bucher, Etienne;Matzke, Antonius J. M.
通讯作者：
Matzke, Antonius J. M.