通过系统分析揭示组蛋白修饰模式与转录因子结合之间的关联
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清华大学生命科学学院,清华大学生命科学学院,清华大学生命科学学院,清华大学生命科学学院,清华大学生命科学学院,清华大学生命科学学院,清华大学生命科学学院

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国家重点基础研究发展计划(973)(2009CB918801),国家自然科学基金(31171274)资助项目


Association of Histone Modification Patterns With Transcription Factor Binding Revealed by Systematic Analysis
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School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University,School of Life Sciences, Tsinghua University

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This work was supported by grants from National Basic Research Program of China (2009CB918801), and The National Natural Science Foundation of China (31171274)

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    摘要:

    转录因子对顺势调控元件的选择性结合,在哺乳动物细胞类型特异的基因表达中扮演重要的角色.这个过程受到染色质表观遗传状态的潜在调控.近期,染色质免疫共沉淀结合测序的研究提供了大量泛基因组水平的数据,阐述转录因子结合以及组蛋白修饰的位点,这为系统地研究转录因子和表观遗传标记之间的空间及调控关系提供了基础. 该研究对公共数据库中的染色质免疫共沉淀结合测序数据进行整合分析,涉及5个细胞系中的85种转录因子、9种组蛋白修饰,目的是研究转录因子结合位点与组蛋白修饰模式以及基因表达在泛基因组水平上的关联.作者发现,不同转录因子与组蛋白修饰的共定位模式高度一致,并且组蛋白修饰在距离转录因子结合位点约500碱基对的位置富集.作者还发现,转录因子结合位点的占有率与活性组蛋白修饰的水平和双峰模式正相关,并且启动子区域组蛋白修饰的双峰和共定位模式和基因的高转录水平相一致.组蛋白修饰模式、转录因子结合位点的占有率与基因转录之间的关联暗示了细胞可能利用的基因表达调控机制.

    Abstract:

    Selective binding of transcription factors (TFs) to cis-regulatory elements plays an important role in cell-type specific gene expression in mammalian cells. This process is potentially guided by epigenetic states of the chromatin. Recent studies provide large amounts of genome-wide ChIP-seq data for both TF binding and histone modification loci, enabling large-scale analysis of spatial and regulatory interplay between TFs and epigenetic marks. In this paper, the authors report an integrative analysis of multiple public ChIP-seq and RNA-seq data sets, concerning 85 TFs, 9 histone modifications and 5 cell lines, to investigate the genome-wide localization correlations between transcription factor binding sites (TFBSs), histone modification patterns and transcription in human. This study reveals that genome-wide co-localization with histone modifications follow the same pattern for different TFs, and active histone marks typically adjoin TFBSs at a distance around 500 bp. TF occupancy at conserved sequences is found positively correlated with levels and bimodal pattern of active histone marks, and the bimodal and co-localized patterns track with higher gene expression. The correlation among histone modification patterns, TF occupancy and gene transcription suggests the existence of a possible regulatory mechanism that cells may implement to regulate transcription.

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李雯,李文婷,曹书娟,余文祥,李文杰,戴俊彪,孙之荣.通过系统分析揭示组蛋白修饰模式与转录因子结合之间的关联[J].生物化学与生物物理进展,2013,40(2):177-187

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历史
  • 收稿日期:2012-04-01
  • 最后修改日期:2012-04-13
  • 接受日期:2012-04-25
  • 在线发布日期: 2013-02-27
  • 出版日期: 2013-02-20