Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment.
Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment.
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DOI：
10.1186/s13059-015-0660-y
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发表时间：
2015-06-11
期刊：
影响因子：
12.3
通讯作者：
Waterland RA
中科院分区：
文献类型：
--
作者：
Silver MJ;Kessler NJ;Hennig BJ;Dominguez-Salas P;Laritsky E;Baker MS;Coarfa C;Hernandez-Vargas H;Castelino JM;Routledge MN;Gong YY;Herceg Z;Lee YS;Lee K;Moore SE;Fulford AJ;Prentice AM;Waterland RA
Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements. The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease. The online version of this article (doi:10.1186/s13059-015-0660-y) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Marabita F;Almgren M;Lindholm ME;Ruhrmann S;Fagerström-Billai F;Jagodic M;Sundberg CJ;Ekström TJ;Teschendorff AE;Tegnér J;Gomez-Cabrero D
通讯作者：
Gomez-Cabrero D
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
12.3
作者：
Lou S;Lee HM;Qin H;Li JW;Gao Z;Liu X;Chan LL;Kl Lam V;So WY;Wang Y;Lok S;Wang J;Ma RC;Tsui SK;Chan JC;Chan TF;Yip KY
通讯作者：
Yip KY
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
12.3
作者：
Liu Y;Siegmund KD;Laird PW;Berman BP
通讯作者：
Berman BP