Antisense transcription-dependent chromatin signature modulates sense transcript dynamics.
Antisense transcription-dependent chromatin signature modulates sense transcript dynamics.
复制标题
DOI：
10.15252/msb.20178007
复制
发表时间：
2018-02-12
影响因子：
9.9
通讯作者：
Mellor J
中科院分区：
文献类型：
--
作者：
Brown T;Howe FS;Murray SC;Wouters M;Lorenz P;Seward E;Rata S;Angel A;Mellor J
反义转录广泛存在于基因组中。尽管基因大小和结构存在很大差异，但我们发现酵母和人类基因共享一个独特的反义转录相关染色质签名。我们想知道这个标记是否与反义转录的生物学功能有关。使用定量RNA-FISH，我们观察到细胞核和细胞质中有义转录物分布的变化，因为反义转录物水平改变。为了确定这些分布背后的机制差异，我们开发了一个数学框架，描述从启动转录到转录降解。在GAL 1，高水平的反义转录改变正义转录动力学，降低转录产物的产生和加工速率，同时增加转录产物的稳定性。这种与转录本稳定性的关系也被观察为全基因组关联。通过破坏Set3C组蛋白去乙酰化酶活性来建立反义转录相关的染色质特征足以类似地改变这些速率，即使在不存在反义转录的情况下。因此，反义转录以染色质依赖性方式改变有义转录动力学。
Antisense transcription is widespread in genomes. Despite large differences in gene size and architecture, we find that yeast and human genes share a unique, antisense transcription‐associated chromatin signature. We asked whether this signature is related to a biological function for antisense transcription. Using quantitative RNA‐FISH, we observed changes in sense transcript distributions in nuclei and cytoplasm as antisense transcript levels were altered. To determine the mechanistic differences underlying these distributions, we developed a mathematical framework describing transcription from initiation to transcript degradation. At GAL1, high levels of antisense transcription alter sense transcription dynamics, reducing rates of transcript production and processing, while increasing transcript stability. This relationship with transcript stability is also observed as a genome‐wide association. Establishing the antisense transcription‐associated chromatin signature through disruption of the Set3C histone deacetylase activity is sufficient to similarly change these rates even in the absence of antisense transcription. Thus, antisense transcription alters sense transcription dynamics in a chromatin‐dependent manner.