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在多个人类和黑猩猩组织中进行的全基因组 DNA 甲基化模式和基因表达水平的研究。

A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.

机构信息

Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

出版信息

PLoS Genet. 2011 Feb;7(2):e1001316. doi: 10.1371/journal.pgen.1001316. Epub 2011 Feb 24.

Abstract

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.

摘要

DNA 的甲基化修饰是一种重要的表观遗传机制,影响着基因表达的时空调控。在许多情况下,包括在不同物种内和跨物种,都已经描述了甲基化模式。然而,甲基化变化在多大程度上可能是物种间基因调控差异的基础,特别是在人类和其他灵长类动物之间,这一点尚未得到研究。为此,我们使用基因组范围的基因表达数据也可获得的组织样本,研究了来自多个人类和黑猩猩的肝脏、心脏和肾脏中的 DNA 甲基化模式。使用多物种基因表达和甲基化数据的 7723 个基因,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,人类和黑猩猩之间的组织间甲基化模式通常是保守的。然而,我们也发现了许多物种之间的基因表达差异,这些差异至少部分可以用相应的甲基化水平差异来解释。特别是,我们估计,在所研究的组织中,启动子甲基化的种间差异可能导致人类和黑猩猩之间高达 12%-18%的基因表达水平差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebd9/3044686/12202520ea6e/pgen.1001316.g001.jpg

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