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Coordinated Effects of Sequence Variation on DNA Binding, Chromatin Structure, and Transcription

机译：序列变异对DNA结合，染色质结构和转录的协同作用

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摘要

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
机译：DNA序列变异与分子表型（如基因表达）的定量变化有关，但其对染色质状态的影响的表征较差。为了了解染色质和基因调控的遗传控制之间的相互作用，我们定量了人类中转录因子结合，组蛋白修饰和基因表达的等位基因变异性。我们在染色质中发现了丰富的等位基因特异性，并且在研究的分子表型之间存在广泛的局部，短程和长程等位基因配位。我们观察到遗传对大多数这些表型的影响，组蛋白修饰表现出强大的上下文相关行为。我们的结果暗示转录因子是基因表达程序的序列特异性调控的主要介体，而组蛋白修饰通常反映了主要调控事件。

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  • 来源
    《Science》 |2013年第6159期|744-747|共4页
  • 作者

    Helena Kilpinen; Sebastian M. Waszak; Andreas R. Gschwind; Sunil K. Raghav; Robert M. Witwicki; Andrea Orioli; Eugenia Migliavacca; Michaeel Wiederkehr; Maria Gutierrez-Arcelus; Mikolaos I. Panousis; Alisa Yurovsky; Tuuli Lappalainen; Luciana Romano-Palumbo; Alexandra Planchon; Deborah Bielser; Julien Bryois; Ismael Padioleau; Gilles Udin; Sarah Thurnheer; David Hacker; Leighton J. Core; John T. Lis; Nouria Hernandez; Alexandre Reymond; Bart Deplancke; Emmanouil T. Dermitzakis;

  • 作者单位

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland;

    Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Protein Expression Core Facility, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Protein Expression Core Facility, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA;

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland;

    Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland;

    Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland,Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland,Institute of Genetics and Genomics of Geneva, University of Geneva, 1211 Geneva, Switzerland,Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia;

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