顶级实验室《Nature》发布人表观遗传图谱

【字体: 时间:2009年10月19日 来源:生物通

编辑推荐:

  生物通报道,Salk研究所基因组分析实验室,Ludwig研究所癌症研究中心,加州大学圣地亚哥分校等处的研究人员绘制了首张人类表观遗传学基因组图谱,相关成果文章Human DNA methylomes at base resolution show widespread epigenomic differences抢先发布在《Nature》在线版上。

  

生物通报道,Salk研究所基因组分析实验室,Ludwig研究所癌症研究中心,加州大学圣地亚哥分校等处的研究人员绘制了首张人类表观遗传学基因组图谱,相关成果文章Human DNA methylomes at base resolution show widespread epigenomic differences抢先发布在《Nature》在线版上。

 

文章通讯作者是Salk研究所的著名教授Joseph R. Ecker,他是国际植物分子生物学和植物基因组学研究领域的著名学者。曾作为主要负责人之一参与了拟南芥全基因组测序工作,拟南芥全基因组功能基因T-DNA文库构建,拟南芥功能基因全长cDNA文库构建,拟南芥全基因组表观遗传学测序工作。同时,Joseph R. Ecker教授在植物激素研究尤其是乙烯信号转导研究方面做出了突出贡献。

 

Joseph R. Ecker带领的研究人员利用功能强大的计算机和新技术绘制了两种人类细胞的表观基因组图谱,它们分别为胚胎干细胞和肺部纤维原细胞。

 

以往,我们仅局限于表观基因组片段图。能够研究表观基因组的全部图谱将方便我们更好地体会基因组究竟如何影响健康和疾病,也可以使我们明白饮食和环境如何作用于基因表达。这一成果将对人类表观遗传学研究作出贡献。

 

这次获得的首张人类表观遗传学基因组图谱包括RNA转录信息,组蛋白修饰信息等内容。

(生物通 小茜)

生物通推荐原文摘要

Human DNA methylomes at base resolution show widespread epigenomic differences

 

Ryan Lister1,9, Mattia Pelizzola1,9, Robert H. Dowen1, R. David Hawkins2, Gary Hon2, Julian Tonti-Filippini4, Joseph R. Nery1, Leonard Lee2, Zhen Ye2, Que-Minh Ngo2, Lee Edsall2, Jessica Antosiewicz-Bourget5,6, Ron Stewart5,6, Victor Ruotti5,6, A. Harvey Millar4, James A. Thomson5,6,7,8, Bing Ren2,3 & Joseph R. Ecker1

 

Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA

Ludwig Institute for Cancer Research,

Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA

ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Crawley, Western Australia 6009, Australia

Morgridge Institute for Research, Madison, Wisconsin 53707, USA

Genome Center of Wisconsin, Madison, Wisconsin 53706, USA

Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA

Department of Anatomy, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

These authors contributed equally to this work.

Correspondence to: Joseph R. Ecker1 Correspondence and requests for materials should be addressed to J.R.E. (Email: ecker@salk.edu).

 

Abstract

DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA–protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non--CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non--CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.

 

Joseph R. Ecker 教授

国际植物分子生物学和植物基因组学研究领域的著名学者。曾作为主要负责人之一参与了拟南芥全基因组测序工作,拟南芥全基因组功能基因T-DNA文库构建,拟南芥功能基因全长cDNA文库构建,拟南芥全基因组表观遗传学测序工作。同时,Joseph R. Ecker教授在植物激素研究尤其是乙烯信号转导研究方面做出了突出贡献。他领导的科研小组所取得的成果处于世界领先水平,在“Cell”、“Science”,“Nature 刊物上发表论文数十篇。

 

代表作:

A complete BAC-based physical map of the Arabidopsis thaliana genome. Nature Genetics, (1999)

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana. Nature, (2000)

Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature, (2000)

Genome-wide Insertional mutagenesis of Arabidopsis thaliana. Science, (2003)

Empirical analysis of transcriptional activity in the Arabidopsis genome. Science, (2003)

Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell, (2006)

Genome-Wide High-Resolution Mapping of Exosome Substrates Reveals Hidden Features in the Arabidopsis Transcriptome. Cell, (2007)

Common Sequence Polymorphisms Shaping Genetic Diversity in Arabidopsis thaliana. Science, (2007)

Highly Integrated Single-Base Resolution Maps of the Epigenome in Arabidopsis. Cell, (2008)

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