Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta.
Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta.
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DOI：
10.1080/15592294.2018.1429857
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Charnock-Jones DS
中科院分区：
文献类型：
--
作者：
Gong S;Johnson MD;Dopierala J;Gaccioli F;Sovio U;Constância M;Smith GC;Charnock-Jones DS
DNA甲基化是基因功能的重要调节因子。胎儿性别与胎盘功能相关的几种特定妊娠并发症的风险有关。然而，胎儿性别和胎盘DNA甲基化之间的关联仍然知之甚少。我们在两名健康女性和两名健康男性孕妇的胎盘中进行了全基因组氧化亚硫酸氢盐测序，产生了25倍的平均基因组覆盖深度。最高排名的差异甲基化区域（DMR）位于X染色体上，但我们在8号染色体上的CUB和Sushi多域1（CSMD 1）基因体内发现了一个225 kb的性别特异性DMR。在该区域中观察到的性别特异性差异甲基化模式使用溶液中靶捕获在另外的胎盘中得到验证。在来自64名女性和67名男性胎盘的新RNA-seq数据集中，CSMD 1 mRNA在男性中比女性胎盘高1.8倍（P值= 8.5 × 10−7，Mann-Whitney检验）。从这131个胎盘CSMD 1 mRNA的外显子水平定量表明，可能的胎盘特异性CSMD 1亚型未检测到在21个体细胞组织分析。我们发现，基因体的常染色体基因，CSMD 1，是差异甲基化的性别和胎盘特异性的方式，胎盘转录丰度显示性别特异性差异。
DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10−7, Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
--
作者：
Fowden, AL;Sibley, C;Constancial, M
通讯作者：
Constancial, M
影响因子：
30.8
作者：
Lappalainen I;Almeida-King J;Kumanduri V;Senf A;Spalding JD;Ur-Rehman S;Saunders G;Kandasamy J;Caccamo M;Leinonen R;Vaughan B;Laurent T;Rowland F;Marin-Garcia P;Barker J;Jokinen P;Torres AC;de Argila JR;Llobet OM;Medina I;Puy MS;Alberich M;de la Torre S;Navarro A;Paschall J;Flicek P
通讯作者：
Flicek P
影响因子：
3.8
作者：
Gaccioli F;Lager S;Sovio U;Charnock-Jones DS;Smith GC
通讯作者：
Smith GC