Genome-wide analysis of the relationships between DNaseI HS, histone modifications and gene expression reveals distinct modes of chromatin domains.
Genome-wide analysis of the relationships between DNaseI HS, histone modifications and gene expression reveals distinct modes of chromatin domains.
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对 DNaseI HS、组蛋白修饰和基因表达之间关系的全基因组分析揭示了染色质结构域的不同模式
DOI：
10.1093/nar/gkr443
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发表时间：
2011-09-01
影响因子：
14.9
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Shu W;Chen H;Bo X;Wang S
为了理解全球转录调控的分子机制，首先必须确定人类基因组中的所有转录调控元件。下一代测序技术的出现为不同物种和特定细胞类型的全基因组分析提供了强大的平台;当与鉴定开放染色质区域[DNA酶I超敏反应（DHS）]或转录因子特异性结合位置[染色质免疫沉淀（ChIP）]的传统技术和来自微阵列的表达数据相结合时，我们将以独特的姿态揭开基因组及其调控的奥秘。为此，我们对来自DNaseI-seq、ChIP-seq和表达阵列的数据之间的关系进行了全球荟萃分析，发现不同细胞类型的调控元件和基因表达之间存在特定的相关性。这些相关性揭示了四种不同模式的染色质结构域结构，反映了不同的功能：抑制，活性，引发和二价。此外，CCCTC结合因子（CTCF）结合位点的基础上，这些综合数据进行了鉴定。我们的研究结果揭示了一个复杂的调控过程，涉及由DNaseI HS位点和组蛋白修饰，并建议这些动态元件可能负责维持染色质结构和完整的人类基因组。我们的综合方法提供了一个例子，通过它可以整合来自不同技术平台的数据，以提供对全球转录调控更有意义的见解。
To understand the molecular mechanisms that underlie global transcriptional regulation, it is essential to first identify all the transcriptional regulatory elements in the human genome. The advent of next-generation sequencing has provided a powerful platform for genome-wide analysis of different species and specific cell types; when combined with traditional techniques to identify regions of open chromatin [DNaseI hypersensitivity (DHS)] or specific binding locations of transcription factors [chromatin immunoprecipitation (ChIP)], and expression data from microarrays, we become uniquely poised to uncover the mysteries of the genome and its regulation. To this end, we have performed global meta-analysis of the relationship among data from DNaseI-seq, ChIP-seq and expression arrays, and found that specific correlations exist among regulatory elements and gene expression across different cell types. These correlations revealed four distinct modes of chromatin domain structure reflecting different functions: repressive, active, primed and bivalent. Furthermore, CCCTC-binding factor (CTCF) binding sites were identified based on these integrative data. Our findings uncovered a complex regulatory process involving by DNaseI HS sites and histone modifications, and suggest that these dynamic elements may be responsible for maintaining chromatin structure and integrity of the human genome. Our integrative approach provides an example by which data from diverse technology platforms may be integrated to provide more meaningful insights into global transcriptional regulation.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
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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
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Ren, Bing
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Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
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Young, Richard A.
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作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
11.8
作者：
Akkers, Robert C.;van Heeringen, Simon J.;Jacobi, Ulrike G.;Janssen-Megens, Eva M.;Francoijs, Kees-Jan;Stunnenberg, Hendrik G.;Veenstra, Gert Jan C.
通讯作者：
Veenstra, Gert Jan C.