Linking the dynamics of chromatin occupancy and transcription with predictive models
Linking the dynamics of chromatin occupancy and transcription with predictive models
复制标题
DOI：
10.1101/2020.06.28.176545
复制
发表时间：
2020-06
期刊：
影响因子：
7
通讯作者：
Trung Q. Tran;Vinay Tripuraneni;Heather K Macalpine;Sneha Mitra;D. MacAlpine;A. Hartemink
中科院分区：
文献类型：
--
作者：
Trung Q. Tran;Vinay Tripuraneni;Heather K Macalpine;Sneha Mitra;D. MacAlpine;A. Hartemink
虽然每个真核细胞内的基因组序列基本上是固定的，但它以复杂和不断变化的染色质状态存在。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（TF）和聚合酶，它们相互作用，与基因组和其他分子相互作用，使染色质能够采取多种可能的构型之一。了解染色质构型的变化如何与转录相关仍然是一个基本的研究问题。我们试图在高时空分辨率的转录和染色质之间的动态相互作用，响应镉胁迫的特点。虽然已经研究了酵母中对环境胁迫的基因调控反应，但染色质状态如何被修饰以及这些修饰如何与基因调控相关联仍然未被探索。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。使用这些签名，我们确定了染色质动态和转录调控之间的关联，不仅为已知的镉反应基因，但在整个基因组，包括反义转录。这些关联使我们能够开发出可推广的模型，可以根据动态染色质签名预测动态转录反应。
Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists in 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. While gene regulatory responses to environmental stress in yeast have been studied, how the chromatin state is modified and how those modifications 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 can predict dynamic transcriptional responses on the basis of dynamic chromatin signatures.