Linking the dynamics of chromatin occupancy and transcription with predictive models.
Linking the dynamics of chromatin occupancy and transcription with predictive models.
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DOI：
10.1101/gr.267237.120
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发表时间：
2021-06
期刊：
影响因子：
7
通讯作者：
Hartemink AJ
中科院分区：
文献类型：
--
作者：
Tran TQ;MacAlpine HK;Tripuraneni V;Mitra S;MacAlpine DM;Hartemink AJ
虽然每个真核细胞内的基因组序列基本上是固定的，但它存在于一个复杂和不断变化的染色质状态中。这种状态部分是由蛋白质与DNA的动态结合决定的。这些蛋白质——包括组蛋白、转录因子（TFs）和聚合酶——相互作用，与基因组和其他分子相互作用，从而使染色质采取极其多种可能的构型之一。了解如何改变染色质结构与转录相关联仍然是一个基本的研究问题。我们试图在高时空分辨率下描述转录和染色质在镉胁迫下的动态相互作用。虽然已经研究了酵母对环境胁迫的基因调控反应，但染色质状态如何变化以及这些变化如何与基因调控联系在一起仍未被探索。通过结合MNase-seq和RNA-seq数据，我们发现了涉及核小体和tf大小的dna结合因子的转录激活和抑制的染色质特征。利用这些特征，我们确定了染色质动力学和转录调控之间的关联，不仅针对已知的镉反应基因，而且针对整个基因组，包括反义转录物。这些关联使我们能够开发出基于动态染色质特征预测动态转录反应的可推广模型。
Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to the DNA. These proteins—including histones, transcription factors (TFs), and polymerases—interact with one another, the genome, and other molecules to allow the chromatin to adopt one of exceedingly many possible configurations. Understanding how changing chromatin configurations associate with transcription remains a fundamental research problem. We sought to characterize at high spatiotemporal resolution the dynamic interplay between transcription and chromatin in response to cadmium stress. Whereas gene regulatory responses to environmental stress in yeast have been studied, how the chromatin state changes and how those changes connect to gene regulation remain unexplored. By combining MNase-seq and RNA-seq data, we found chromatin signatures of transcriptional activation and repression involving both nucleosomal and TF-sized DNA-binding factors. Using these signatures, we identified associations between chromatin dynamics and transcriptional regulation, not only for known cadmium response genes, but across the entire genome, including antisense transcripts. Those associations allowed us to develop generalizable models that predict dynamic transcriptional responses on the basis of dynamic chromatin signatures.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
64.8
作者：
Brogaard, Kristin;Xi, Liqun;Wang, Ji-Ping;Widom, Jonathan
通讯作者：
Widom, Jonathan
影响因子：
64.5
作者：
Geisberg JV;Moqtaderi Z;Fan X;Ozsolak F;Struhl K
通讯作者：
Struhl K
影响因子：
3.6
作者：
Boy-Marcotte, E;Lagniel, G;Labarre, J
通讯作者：
Labarre, J
影响因子：
3.2
作者：
Kawahata, Miho;Masaki, Kazuo;Iefuji, Haruyuki
通讯作者：
Iefuji, Haruyuki