Natural variation of histone modification and its impact on gene expression in the rat genome.
Natural variation of histone modification and its impact on gene expression in the rat genome.
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组蛋白修饰的自然变异及其对大鼠基因组基因表达的影响。
DOI：
10.1101/gr.169029.113
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发表时间：
2014-06
期刊：
影响因子：
7
通讯作者：
Hubner N
中科院分区：
文献类型：
--
作者：
Rintisch C;Heinig M;Bauerfeind A;Schafer S;Mieth C;Patone G;Hummel O;Chen W;Cook S;Cuppen E;Colomé-Tatché M;Johannes F;Jansen RC;Neil H;Werner M;Pravenec M;Vingron M;Hubner N
组蛋白修饰是表观遗传标记，在许多生物过程中发挥基础作用，包括控制染色质介导的基因表达调控。关于基因组中组蛋白修饰水平的个体间变异性以及它们受遗传变异影响的程度，人们知之甚少。我们用组蛋白修饰图标注了大鼠基因组，确定了不同品系之间组蛋白三甲基赖氨酸水平的差异，并在一组大鼠重组近交系及其祖先品系的心脏和肝脏组织中使用CHIP-SEQ在基因组水平上描述了它们潜在的遗传基础。我们确定了组蛋白甲基化水平在个体之间的广泛差异，并定位了整个基因组中数百个潜在的顺式和反式作用基因，这些基因以等位基因特异性的方式调节组蛋白甲基化水平。有趣的是，大多数组蛋白甲基化水平的变异是连锁的，所发现的最显著的QTL影响心脏基因组中899个推定启动子的H3K4me3水平。心脏和肝脏中不同转录因子的结合部位富含顺式作用变异。DNA变异与组蛋白甲基化和基因表达水平的综合分析表明，组蛋白QTL是基因表达的重要预测因子，联合分析显著增强了对基因表达性状(EQTL)的预测。我们的数据表明，遗传变异对组蛋白三甲基化标记有广泛的影响，这可能有助于揭示新的基因型-表型关系。
Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains. We identified extensive variation of histone methylation levels among individuals and mapped hundreds of underlying cis- and trans-acting loci throughout the genome that regulate histone methylation levels in an allele-specific manner. Interestingly, most histone methylation level variation was trans-linked and the most prominent QTL identified influenced H3K4me3 levels at 899 putative promoters throughout the genome in the heart. Cis- acting variation was enriched in binding sites of distinct transcription factors in heart and liver. The integrated analysis of DNA variation together with histone methylation and gene expression levels showed that histoneQTLs are an important predictor of gene expression and that a joint analysis significantly enhanced the prediction of gene expression traits (eQTLs). Our data suggest that genetic variation has a widespread impact on histone trimethylation marks that may help to uncover novel genotype–phenotype relationships.
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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.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
7
作者：
Atanur, Santosh S.;Birol, Inanc;Aitman, Timothy J.
通讯作者：
Aitman, Timothy J.
影响因子：
64.8
作者：
通讯作者：
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