Genetic determinants of co-accessible chromatin regions in activated T cells across humans.
Genetic determinants of co-accessible chromatin regions in activated T cells across humans.
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DOI：
10.1038/s41588-018-0156-2
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发表时间：
2018-08
期刊：
影响因子：
30.8
通讯作者：
Regev A
中科院分区：
文献类型：
--
作者：
Gate RE;Cheng CS;Aiden AP;Siba A;Tabaka M;Lituiev D;Machol I;Gordon MG;Subramaniam M;Shamim M;Hougen KL;Wortman I;Huang SC;Durand NC;Feng T;De Jager PL;Chang HY;Aiden EL;Benoist C;Beer MA;Ye CJ;Regev A
超过90%与复杂人类性状相关的遗传变异定位在非编码区域，但对于它们如何在健康和疾病中调节基因调控却知之甚少。一种可能的机制是，遗传变异影响一个或多个顺式调控元件的活性，导致特定细胞类型中的基因表达变异。为了识别此类情况，我们分析了来自多达105名健康捐赠者的经刺激的原代CD4 + T细胞的ATAC - seq和RNA - seq图谱。我们发现可接近的染色质区域（ATAC峰）在千碱基和百万碱基分辨率下是共同可接近的，这与通过T细胞中的原位Hi - C测量的3D染色质组织一致。位于ATAC峰内的15%的遗传变异影响了相应峰的可接近性（ATAC - QTLs）。ATAC - QTLs对共同可接近的峰影响最大，与基因表达相关，并且自身免疫疾病变异富集。我们的结果为自然遗传变异如何单独或协同调节顺式调控元件以影响基因表达提供了见解。
Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the 3D chromatin organization measured by in situ Hi-C in T cells. 15% of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (ATAC-QTLs). ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression, and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.
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影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
6.5
作者：
Fan, Yang-Yi;Monk, Jennifer M.;Chapkin, Robert S.
通讯作者：
Chapkin, Robert S.