A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.
A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.
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DOI：
10.1371/journal.pgen.1001316
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发表时间：
2011-02
期刊：
影响因子：
4.5
通讯作者：
Gilad Y
中科院分区：
文献类型：
--
作者：
Pai AA;Bell JT;Marioni JC;Pritchard JK;Gilad Y
DNA甲基化修饰是影响基因表达时空调控的重要表观遗传机制。甲基化模式已在许多情况下描述的范围内和跨物种。然而，甲基化的变化在多大程度上可能是基因调控的物种间差异的基础，特别是人类和其他灵长类动物之间的差异，尚未研究。为此，我们研究了来自多个人类和黑猩猩的肝脏、心脏和肾脏的DNA甲基化模式，使用的组织样本也有全基因组基因表达数据。利用7，723个基因的多物种基因表达和甲基化数据，我们能够研究启动子DNA甲基化在跨组织和物种的基因调控进化中的作用。我们发现组织间甲基化模式在人类和黑猩猩之间通常是保守的。然而，我们也发现了大量的物种之间的基因表达差异，这可能是解释，至少在一定程度上，相应的差异甲基化水平。特别是，我们估计，在我们研究的组织中，启动子甲基化的物种间差异可能是人类和黑猩猩之间基因表达水平差异的12%-18%。长期以来，人们一直假设基因调控的变化在灵长类进化中发挥了重要作用。然而，尽管有丰富的比较基因表达数据，仍然只有少数研究，重点是在基因调控的灵长类动物之间的差异的机制。特别是，我们对表观遗传图谱的变化在多大程度上可以解释灵长类动物之间基因表达水平的差异知之甚少。为此，我们研究了多个人类和黑猩猩肝脏、心脏和肾脏中的DNA甲基化和基因表达水平。使用这些比较数据，我们能够研究基因调控的进化，在整个组织和物种的DNA甲基化谱的保护或变化的背景下。我们发现组织间甲基化模式在人类和黑猩猩之间通常是保守的。此外，我们还发现了物种之间的大量基因表达差异，这可能至少部分地由甲基化水平的相应差异来解释。我们估计，在我们研究的组织中，甲基化水平的物种间差异可能是人类和黑猩猩之间基因表达水平差异的12%-18%。
The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied. To this end, we studied DNA methylation patterns in livers, hearts, and kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data were also available. Using the multi-species gene expression and methylation data for 7,723 genes, we were able to study the role of promoter DNA methylation in the evolution of gene regulation across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. However, we also found a large number of gene expression differences between species that might be explained, at least in part, by corresponding differences in methylation levels. In particular, we estimate that, in the tissues we studied, inter-species differences in promoter methylation might underlie as much as 12%–18% of differences in gene expression levels between humans and chimpanzees. It has long been hypothesized that changes in gene regulation have played an important role in primate evolution. However, despite the wealth of comparative gene expression data, there are still only few studies that focus on the mechanisms underlying inter-primate differences in gene regulation. In particular, we know relatively little about the degree to which changes in epigenetic profiles might explain differences in gene expression levels between primates. To this end, we studied DNA methylation and gene expression levels in livers, hearts, and kidneys from multiple humans and chimpanzees. Using these comparative data, we were able to study the evolution of gene regulation in the context of conservation of or changes in DNA methylation profiles across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. In addition, we also found a large number of gene expression differences between species, which might be explained, at least in part, by corresponding differences in methylation levels. We estimate that, in the tissues we studied, inter-species differences in methylation levels might underlie as much as 12%–18% of differences in gene expression levels between humans and chimpanzees.
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影响因子：
7
作者：
Blekhman, Ran;Marioni, John C.;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
3.3
作者：
Blekhman, Ran;Oshlack, Alicia;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
10.5
作者：
Berger, Shelley L.;Kouzarides, Tony;Shilatifard, Ali
通讯作者：
Shilatifard, Ali
影响因子：
3.7
作者：
Goren, Alon;Simchen, Giora;Fibach, Eitan;Szabo, Piroska E.;Tanimoto, Keiji;Chakalova, Lyubomira;Pfeifer, Gerd P.;Fraser, Peter J.;Engel, James D.;Cedar, Howard
通讯作者：
Cedar, Howard
DOI：
10.1073/pnas.87.11.4174
发表时间：
1990-06-01
影响因子：
11.1
作者：
HANSEN, RS;GARTLER, SM
通讯作者：
GARTLER, SM