Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.
Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.
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高原缺氧适应的染色质可达性景观和调控网络
DOI：
10.1038/s41467-020-18638-8
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发表时间：
2020-10-01
影响因子：
16.6
通讯作者：
Su B
中科院分区：
文献类型：
--
作者：
Xin J;Zhang H;He Y;Duren Z;Bai C;Chen L;Luo X;Yan DS;Zhang C;Zhu X;Yuan Q;Feng Z;Cui C;Qi X;Ouzhuluobu;Wong WH;Wang Y;Su B
先前的全基因组扫描发现许多非编码变异在选择下，这表明迫切需要了解非编码调控元件（REs）的功能作用。在这里，我们生成了缺氧和常压条件下培养HUVECs的配对ATAC-seq和RNA-seq数据的时间过程。我们进一步开发了一种变异解释方法（vPECA）来识别活性选择REs （ASREs）和相关的监管网络。这些snp降低了ASREs的可及性，减弱了相关tf的结合强度，协同下调了epas1的表达。我们进一步构建了fepas1的下游网络，阐明了其在缺氧反应和血管生成中的作用。总的来说，我们提供了一种系统的方法来解释在适当的细胞类型和相关的动态条件下表型相关的非编码变异，以模拟它们对基因调控的影响。
High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs ofEPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulateEPAS1expression. We further construct the downstream network ofEPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.
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影响因子：
16.6
作者：
Gräf S;Haimel M;Bleda M;Hadinnapola C;Southgate L;Li W;Hodgson J;Liu B;Salmon RM;Southwood M;Machado RD;Martin JM;Treacy CM;Yates K;Daugherty LC;Shamardina O;Whitehorn D;Holden S;Aldred M;Bogaard HJ;Church C;Coghlan G;Condliffe R;Corris PA;Danesino C;Eyries M;Gall H;Ghio S;Ghofrani HA;Gibbs JSR;Girerd B;Houweling AC;Howard L;Humbert M;Kiely DG;Kovacs G;MacKenzie Ross RV;Moledina S;Montani D;Newnham M;Olschewski A;Olschewski H;Peacock AJ;Pepke-Zaba J;Prokopenko I;Rhodes CJ;Scelsi L;Seeger W;Soubrier F;Stein DF;Suntharalingam J;Swietlik EM;Toshner MR;van Heel DA;Vonk Noordegraaf A;Waisfisz Q;Wharton J;Wort SJ;Ouwehand WH;Soranzo N;Lawrie A;Upton PD;Wilkins MR;Trembath RC;Morrell NW
通讯作者：
Morrell NW
影响因子：
30.8
作者：
Germain, Marine;Eyries, Melanie;Montani, David;Poirier, Odette;Girerd, Barbara;Dorfmueller, Peter;Coulet, Florence;Nadaud, Sophie;Maugenre, Svetlana;Guignabert, Christophe;Carpentier, Wassila;Vonk-Noordegraaf, Anton;Levy, Marilyne;Chaouat, Ari;Lambert, Jean-Charles;Bertrand, Marion;Dupuy, Anne-Marie;Letenneur, Luc;Lathrop, Mark;Amouyel, Philippe;de Ravel, Thomy J. L.;Delcroix, Marion;Austin, Eric D.;Robbins, Ivan M.;Hemnes, Anna R.;Loyd, James E.;Berman-Rosenzweig, Erika;Barst, Robyn J.;Chung, Wendy K.;Simonneau, Gerald;Tregouet, David A.;Humbert, Marc;Soubrier, Florent
通讯作者：
Soubrier, Florent
影响因子：
20.1
作者：
Casanello, P;Torres, A;Sobrevia, L
通讯作者：
Sobrevia, L
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
影响因子：
2.9
作者：
Butaric, Lauren N.;Klocke, Ross P.
通讯作者：
Klocke, Ross P.