Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients.
Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients.
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DOI：
10.1371/journal.pone.0206511
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Barcellos LF
中科院分区：
文献类型：
--
作者：
Rhead B;Brorson IS;Berge T;Adams C;Quach H;Moen SM;Berg-Hansen P;Celius EG;Sangurdekar DP;Bronson PG;Lea RA;Burnard S;Maltby VE;Scott RJ;Lechner-Scott J;Harbo HF;Bos SD;Barcellos LF
DNA甲基化是一种受环境因素影响的表观遗传标记，与基因表达和表型的变化有关。它可能将环境暴露与疾病病因联系起来，或指示参与疾病发病机制的重要基因通路。我们鉴定了复发缓解型多发性硬化症（MS）患者与健康对照组相比T细胞中甲基化差异的基因组区域。在从94名MS女性和94名健康女性的外周血中纯化的CD 4+和CD 8 + T细胞中的450，000个基因组位点处评估DNA甲基化，并使用bumphunter鉴定差异甲基化区域。在四个位点附近观察到差异DNA甲基化：MOG/ZFP 57、HLA-DRB 1、NINJ 2/LOC 100049716和SLFN 12。在两种T细胞亚型中均观察到SLFN 12基因第一外显子的甲基化增加，并且在限制分析从未接受治疗或停止治疗超过2.5年的患者样本后仍然存在。研究人员评估了T细胞中差异甲基化区域附近的基因在1，329名MS女性和97名健康女性的全血样本中的差异表达。与对照组相比，观察到MS患者全血中HLA-DRB 1、NINJ 2和SLFN 12的基因表达降低。我们得出结论，MS患者的T细胞显示与对照组相比差异DNA甲基化的区域，并且在全血中观察到相应的基因表达差异。显示甲基化和表达差异的两个基因，NINJ 2和SLFN 12，以前没有涉及MS。SLFN 12是进一步研究的一个特别引人注目的目标，因为已知该基因在T细胞活化期间下调，并被用于治疗MS的I型干扰素（IFN）上调。
DNA methylation is an epigenetic mark that is influenced by environmental factors and is associated with changes to gene expression and phenotypes. It may link environmental exposures to disease etiology or indicate important gene pathways involved in disease pathogenesis. We identified genomic regions that are differentially methylated in T cells of patients with relapsing remitting multiple sclerosis (MS) compared to healthy controls. DNA methylation was assessed at 450,000 genomic sites in CD4+ and CD8+ T cells purified from peripheral blood of 94 women with MS and 94 healthy women, and differentially methylated regions were identified using bumphunter. Differential DNA methylation was observed near four loci: MOG/ZFP57, HLA-DRB1, NINJ2/LOC100049716, and SLFN12. Increased methylation of the first exon of the SLFN12 gene was observed in both T cell subtypes and remained present after restricting analyses to samples from patients who had never been on treatment or had been off treatment for more than 2.5 years. Genes near the regions of differential methylation in T cells were assessed for differential expression in whole blood samples from a separate population of 1,329 women with MS and 97 healthy women. Gene expression of HLA-DRB1, NINJ2, and SLFN12 was observed to be decreased in whole blood in MS patients compared to controls. We conclude that T cells from MS patients display regions of differential DNA methylation compared to controls, and corresponding gene expression differences are observed in whole blood. Two of the genes that showed both methylation and expression differences, NINJ2 and SLFN12, have not previously been implicated in MS. SLFN12 is a particularly compelling target of further research, as this gene is known to be down-regulated during T cell activation and up-regulated by type I interferons (IFNs), which are used to treat MS.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
5.4
作者：
Kaskow, Belinda J.;Baecher-Allan, Clare
通讯作者：
Baecher-Allan, Clare
影响因子：
5.8
作者：
Aryee, Martin J.;Jaffe, Andrew E.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.