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Regulatory analysis of the C. elegans genome with spatiotemporal resolution

机译:线虫基因组的时空分辨率调控分析

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摘要

Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatio-temporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.%在这篇论文中, "modENCODE consortium"对线虫发育多个阶段的92个转录因子和调控蛋白的结合点的基因组分布进行了研究。通过对这些数据和细胞分辨率的表达数据进行整合, 他们生成了后生动物转录因子结合点的一个时空分布图, 该图被用来研究发育调控线路的设计和性质。
机译:以细胞和时间分辨率发现基因组中转录调控事件的结构和动力学,对于理解发育和疾病的调控基础至关重要。我们通过进行241 ChIP-seq(染色质免疫沉淀,然后测序)实验,确定了秀丽隐杆线虫发育多个阶段中92个转录因子和调控蛋白结合位点的基因组分布。监管绑定和细胞分辨率表达数据的整合产生了时空分辨的后生转录因子结合图。使用此图,我们探索在编码因子的共结合和共表达水平上编码组合逻辑的发育调控电路,表征调控结合的基因组覆盖和聚类,转录的结合偏好以及受转录调控的生物学过程因子,全局转录因子共关联和基因组亚域,它们提示了共同的调控模式,并确定了关键转录因子和转录因子共关联,用于确定各个谱系和细胞类型的命运。%在这篇论文中,“ modENCODE财团“对线虫发育多个阶段的92个转录因子和重组蛋白的结合点的基因组分布进行了研究。”通过对这些数据和细胞分辨率的表达数据进行整合,他们生成了后生动物转录因子结合点的一个时空分布图,该图被用来研究开发扩展线路的设计和性质。

著录项

  • 来源
    《Nature》 |2014年第7515期|400-405337|共7页
  • 作者单位

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

    Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;

    Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;

    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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