Chromatin Looping Links Target Genes with Genetic Risk Loci for Dermatological Traits.
Chromatin Looping Links Target Genes with Genetic Risk Loci for Dermatological Traits.
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DOI：
10.1016/j.jid.2021.01.015
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Orozco G
中科院分区：
文献类型：
--
作者：
Shi C;Ray-Jones H;Ding J;Duffus K;Fu Y;Gaddi VP;Gough O;Hankinson J;Martin P;McGovern A;Yarwood A;Gaffney P;Eyre S;Rattray M;Warren RB;Orozco G
调控元件和基因启动子之间的染色质循环提出了一种潜在的机制，疾病风险变体影响其靶基因。在这项研究中，我们使用H3K27ac HiChIP，一种用于测定两种细胞系中活性染色质相互作用组的方法：角质形成细胞和皮肤淋巴瘤衍生的CD8+ T细胞。我们整合了淋巴母细胞系和原代CD4+ T细胞的公共数据集，并确定了皮肤相关疾病风险位点的基因靶点。相互作用的基因丰富了每个性状中已知重要性的途径，如细胞因子反应（银屑病关节炎和银屑病）和复制性衰老（黑色素瘤）。我们展示了我们的分析如何为当前对多种银屑病相关风险位点的理解提供信息的例子。例如，在我们的数据集中，通常被分配给IFNLR1的变体rs10794648与皮肤修复和发育所必需的基因GRHL3相关联。因此，我们的研究结果表明皮肤相关因素在疾病风险中的重要性。
Chromatin looping between regulatory elements and gene promoters presents a potential mechanism whereby disease risk variants affect their target genes. In this study, we use H3K27ac HiChIP, a method for assaying the active chromatin interactome in two cell lines: keratinocytes and skin lymphoma–derived CD8+ T cells. We integrate public datasets for a lymphoblastoid cell line and primary CD4+ T cells and identify gene targets at risk loci for skin-related disorders. Interacting genes enrich for pathways of known importance in each trait, such as cytokine response (psoriatic arthritis and psoriasis) and replicative senescence (melanoma). We show examples of how our analysis can inform changes in the current understanding of multiple psoriasis-associated risk loci. For example, the variant rs10794648, which is generally assigned to IFNLR1, was linked to GRHL3, a gene essential in skin repair and development, in our dataset. Our findings, therefore, indicate a renewed importance of skin-related factors in the risk of disease.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
12.3
作者：
Burren OS;Rubio García A;Javierre BM;Rainbow DB;Cairns J;Cooper NJ;Lambourne JJ;Schofield E;Castro Dopico X;Ferreira RC;Coulson R;Burden F;Rowlston SP;Downes K;Wingett SW;Frontini M;Ouwehand WH;Fraser P;Spivakov M;Todd JA;Wicker LS;Cutler AJ;Wallace C
通讯作者：
Wallace C
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
7
作者：
Dryden NH;Broome LR;Dudbridge F;Johnson N;Orr N;Schoenfelder S;Nagano T;Andrews S;Wingett S;Kozarewa I;Assiotis I;Fenwick K;Maguire SL;Campbell J;Natrajan R;Lambros M;Perrakis E;Ashworth A;Fraser P;Fletcher O
通讯作者：
Fletcher O