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Comparative analysis of regulatory information and circuits across distant species

机译：远距离物种监管信息和回路的比较分析

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摘要

果蝇和蠕虫长期以来作为人类生物学的重要模型动物被加以研究。此前, 基因调控的保守性主要是通过关注个别要素和因子被研究的。"modENCODE consortium"的目标是对转录调控特征的基本原理进行一个大规模的比较分析。在这篇论文中, 作者对165个人类的、93个蠕虫的和52个果蝇的转录调控因子在不同细胞类型、发育阶段或条件下的全基因组结合位置进行了标绘。他们发现, 总体上, 以前对个别因子所观察到的基因调控性质是后生动物调控的普遍原理, 这些性质保持得非常好, 尽管个别网络连接存在广泛的功能分歧。调控线路的这些比较图, 将可帮助我们了解现代有机体生物学的调控机制与人类生物学、发育和疾病有什么关系。%Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1, 019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regu­latory networks are remarkably conserved and that orthologous reg­ulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual net­work connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regula­tory underpinnings of model organism biology and how these relate to human biology, development and disease.
机译：果蝇和蠕虫长期以来作为人类生物学的重要模型动物被加以研究。此前, 基因调控的保守性主要是通过关注个别要素和因子被研究的。"modENCODE consortium"的目标是对转录调控特征的基本原理进行一个大规模的比较分析。在这篇论文中, 作者对165个人类的、93个蠕虫的和52个果蝇的转录调控因子在不同细胞类型、发育阶段或条件下的全基因组结合位置进行了标绘。他们发现, 总体上, 以前对个别因子所观察到的基因调控性质是后生动物调控的普遍原理, 这些性质保持得非常好, 尽管个别网络连接存在广泛的功能分歧。调控线路的这些比较图, 将可帮助我们了解现代有机体生物学的调控机制与人类生物学、发育和疾病有什么关系。%Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1, 019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regu­latory networks are remarkably conserved and that orthologous reg­ulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual net­work connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regula­tory underpinnings of model organism biology and how these relate to human biology, development and disease.

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  • 来源
    《Nature》 |2014年第7515期|453-456339|共5页
  • 作者

    Alan P. Boyle; Carlos L. Araya; Cathleen Brdlik; Philip Cayting; Chao Cheng; et al;

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

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

    Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, 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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