A map of the cis-regulatory sequences in the mouse genome.
A map of the cis-regulatory sequences in the mouse genome.
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DOI：
10.1038/nature11243
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发表时间：
2012-08-02
期刊：
影响因子：
64.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Shen, Yin;Yue, Feng;McCleary, David F.;Ye, Zhen;Edsall, Lee;Kuan, Samantha;Wagner, Ulrich;Dixon, Jesse;Lee, Leonard;Lobanenkov, Victor V.;Ren, Bing
实验小鼠是生物医学研究中应用最广泛的哺乳动物模式生物。小鼠基因组的2.6 × 10个碱基与人类基因组具有高度的保守性，因此对小鼠基因组的全面注释将对理解人类基因组的功能具有重要价值。到目前为止，小鼠基因组中的大部分功能序列尚未被发现，特别是顺式调控序列的注释仍然很差。比较基因组学是发现这些序列的有力工具，但它本身不能解决它们的时间和空间功能。最近，ChIP-Seq已被开发用于鉴定几种生物基因组中的顺式调控元件，包括人类、黑腹果蝇和秀丽隐杆线虫。在这里，我们将相同的实验方法应用于小鼠的19种不同的组织和细胞类型，以产生近30万个小鼠顺式调控序列的图谱。加注释的序列占小鼠基因组的11%，其中包括70%以上的保守非编码序列。我们定义了组织特异性增强子，并确定了每种组织或细胞类型中调节基因表达的潜在转录因子。最后，我们表明，许多小鼠基因组被组织到协调调节的增强子和启动子域。我们的研究结果为哺乳动物基因组功能元件的注释和组织特异性基因表达调控机制的研究提供了资源。
The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 10 bases of the mouse genome possess a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences, but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized in to domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
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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：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
影响因子：
64.5
作者：
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing
通讯作者：
Ren, Bing