Identification of cis regulatory features in the embryonic zebrafish genome through large-scale profiling of H3K4me1 and H3K4me3 binding sites.
Identification of cis regulatory features in the embryonic zebrafish genome through large-scale profiling of H3K4me1 and H3K4me3 binding sites.
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DOI：
10.1016/j.ydbio.2011.03.007
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发表时间：
2011-09-15
影响因子：
2.7
通讯作者：
Lawson ND
中科院分区：
文献类型：
--
作者：
Aday AW;Zhu LJ;Lakshmanan A;Wang J;Lawson ND
生物体的基因组序列是细胞功能所必需的蛋白质和调控RNA的蓝图。基因组还含有控制基因表达的顺式作用非编码序列，对于协调胚胎发育过程中的调控程序至关重要。然而，多细胞生物体中不同细胞类型的基因组序列基本相同，这表明DNA可及性和染色质结构等因素在调控细胞特异性基因表达方面发挥着至关重要的作用。最近的研究已经确定了特定的染色质修饰，它们定义了功能上不同的顺式调节元件。在这些形式中，组蛋白3在赖氨酸4(分别为H3K4me1或H3K4me3)处单甲基化或三甲基化，优先与哺乳动物基因组中的启动子和增强子元件结合。在这项工作中，我们研究了这些修饰的组蛋白是否能够类似地识别斑马鱼基因组中的顺式调控元件。通过染色质免疫沉淀和深度测序，我们发现H3K4me1和H3K4me3在斑马鱼发育中的基因组转录起始处富含，并且这种关联与基因表达有关。我们进一步发现，这些修饰与包括已知的活性增强子在内的远端非编码保守元件有关。最后，我们证明了利用H3K4me1和H3K4me3结合谱结合现有的表达数据来计算识别发育中胚胎中同步表达基因两侧的相关顺式调控序列是可能的。综上所述，我们的结果表明，H3K4me1和H3K4me3通常标记斑马鱼基因组中的顺式调控元件，并表明使用该方法进一步表征斑马鱼将被证明在确定该模型系统中的转录网络方面有价值。
An organism’s genome sequence serves as a blueprint for the proteins and regulatory RNAs essential for cellular function. The genome also harbors cis-acting non-coding sequences that control gene expression and are essential to coordinate regulatory programs during embryonic development. However, the genome sequence is largely identical between cell types within a multi-cellular organism indicating that factors such as DNA accessibility and chromatin structure play a crucial role in governing cell-specific gene expression. Recent studies have identified particular chromatin modifications that define functionally distinct cis regulatory elements. Among these are forms of histone 3 that are mono- or tri-methylated at lysine 4 (H3K4me1 or H3K4me3, respectively), which bind preferentially to promoter and enhancer elements in the mammalian genome. In this work, we investigated whether these modified histones could similarly identify cis regulatory elements within the zebrafish genome. By applying chromatin immunoprecipitation followed by deep sequencing, we find that H3K4me1 and H3K4me3 are enriched at transcriptional start sites in the genome of the developing zebrafish embryo and that this association correlates with gene expression. We further find that these modifications associate with distal non-coding conserved elements, including known active enhancers. Finally, we demonstrate that it is possible to utilize H3K4me1 and H3K4me3 binding profiles in combination with available expression data to computationally identify relevant cis regulatory sequences flanking syn-expressed genes in the developing embryo. Taken together, our results indicate that H3K4me1 and H3K4me3 generally mark cis regulatory elements within the zebrafish genome and indicate that further characterization of the zebrafish using this approach will prove valuable in defining transcriptional networks in this model system.
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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：
64.8
作者：
Davidson, AJ;Ernst, P;Zon, LI
通讯作者：
Zon, LI
影响因子：
10.5
作者：
BAILEY, AM;POSAKONY, JW
通讯作者：
POSAKONY, JW
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.
Galaxy：一种基于Web的基因组分析工具。
影响因子：
--
作者：
Blankenberg, Daniel;Von Kuster, Gregory;Coraor, Nathaniel;Ananda, Guruprasad;Lazarus, Ross;Mangan, Mary;Nekrutenko, Anton;Taylor, James
通讯作者：
Taylor, James