Chromatin landscapes and genetic risk in systemic lupus.
Chromatin landscapes and genetic risk in systemic lupus.
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DOI：
10.1186/s13075-016-1169-9
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
Jarvis JN
中科院分区：
文献类型：
--
作者：
Hui-Yuen JS;Zhu L;Wong LP;Jiang K;Chen Y;Liu T;Jarvis JN
系统性红斑狼疮（SLE）是一种多系统、复杂的疾病，其中环境与遗传基因相互作用产生具有个体间变异性的广泛表型。在最近的全基因组关联研究中，46个单核苷酸多态性（SNPs）显示与SLE遗传风险有关，其中30个位于人类基因组的非编码区域。因此，我们试图识别和描述位于这些感兴趣区域内的功能元件（除了基因）。我们使用染色质免疫沉淀法和测序法鉴定了成人中性粒细胞中与增强子功能相关的表观遗传标记，以确定增强子相关的组蛋白标记是否在包含46个感兴趣的snp的连锁不平衡（LD）区中富集。我们还查询了CD4+ T细胞和CD19+ B细胞的表观基因组学路线图数据，以确定淋巴样细胞中这些相同的元素。与基因组背景相比，所有三种细胞类型都显示了增强子相关组蛋白标记在由slel相关snp编码的LD块中的富集。此外，在这些LD块的启动子区域内，所有三种细胞类型都显示出高于基因组背景的转录因子结合位点的富集。在CD19+ B细胞中，除一个外，所有感兴趣的LD块也富集了增强子相关的组蛋白标记。SLE的大部分遗传风险存在于疾病相关细胞的基因组区域内或附近，这些区域富含与增强子功能相关的表观遗传标记。阐明这些非编码元件在这些细胞类型特异性基因组中的具体作用将对我们理解SLE发病机制至关重要。本文的在线版本（doi:10.1186/s13075-016-1169-9）包含补充材料，可供授权用户使用。
Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest. We used chromatin immunoprecipitation followed by sequencing to identify epigenetic marks associated with enhancer function in adult neutrophils to determine whether enhancer-associated histone marks were enriched within the linkage disequilibrium (LD) blocks encompassing the 46 SNPs of interest. We also interrogated available data in Roadmap Epigenomics for CD4+ T cells and CD19+ B cells to identify these same elements in lymphoid cells. All three cell types demonstrated enrichment of enhancer-associated histone marks compared with genomic background within LD blocks encoded by SLE-associated SNPs. In addition, within the promoter regions of these LD blocks, all three cell types demonstrated enrichment for transcription factor binding sites above genomic background. In CD19+ B cells, all but one of the LD blocks of interest were also enriched for enhancer-associated histone marks. Much of the genetic risk for SLE lies within or near genomic regions of disease-relevant cells that are enriched for epigenetic marks associated with enhancer function. Elucidating the specific roles of these noncoding elements within these cell-type-specific genomes will be crucial to our understanding of SLE pathogenesis. The online version of this article (doi:10.1186/s13075-016-1169-9) contains supplementary material, which is available to authorized users.
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DOI：
10.1002/art.39499
发表时间：
2016-04
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Ichinose K;Ushigusa T;Nishino A;Nakashima Y;Suzuki T;Horai Y;Koga T;Kawashiri SY;Iwamoto N;Tamai M;Arima K;Nakamura H;Obata Y;Yamamoto K;Origuchi T;Nishino T;Kawakami A;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
DOI：
10.1196/annals.1423.015
发表时间：
2007-01-01
期刊：
AUTOIMMUNITY, PT B: NOVEL APPLICATIONS OF BASIC RESEARCH
影响因子：
--
作者：
Cervino, Alessandra C. L.;Tsinoremas, Nicholas E.;Hoffman, Robert W.
通讯作者：
Hoffman, Robert W.
影响因子：
5.8
作者：
Dozmorov MG;Dominguez N;Bean K;Macwana SR;Roberts V;Glass E;James JA;Guthridge JM
通讯作者：
Guthridge JM