The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
Genome Res. 2020 Dec;30(12):1752-1765. doi: 10.1101/gr.265934.120. Epub 2020 Oct 22.
RNA profiling has provided increasingly detailed knowledge of gene expression patterns, yet the different regulatory architectures that drive them are not well understood. To address this, we profiled and compared transcriptional and regulatory element activities across five tissues of , covering ∼90% of cells. We find that the majority of promoters and enhancers have tissue-specific accessibility, and we discover regulatory grammars associated with ubiquitous, germline, and somatic tissue-specific gene expression patterns. In addition, we find that germline-active and soma-specific promoters have distinct features. Germline-active promoters have well-positioned +1 and -1 nucleosomes associated with a periodic 10-bp WW signal (W = A/T). Somatic tissue-specific promoters lack positioned nucleosomes and this signal, have wide nucleosome-depleted regions, and are more enriched for core promoter elements, which largely differ between tissues. We observe the 10-bp periodic WW signal at ubiquitous promoters in other animals, suggesting it is an ancient conserved signal. Our results show fundamental differences in regulatory architectures of germline and somatic tissue-specific genes, uncover regulatory rules for generating diverse gene expression patterns, and provide a tissue-specific resource for future studies.
RNA 谱分析为基因表达模式提供了越来越详细的知识,但驱动这些模式的不同调控结构还没有得到很好的理解。为了解决这个问题,我们对 进行了分析和比较,涵盖了五个组织中的转录和调控元件活性,涵盖了大约 90%的细胞。我们发现大多数启动子和增强子都具有组织特异性的可及性,并且我们发现了与普遍存在的、生殖系和体细胞特异性基因表达模式相关的调控语法。此外,我们发现生殖系活性和体细胞特异性启动子具有不同的特征。生殖系活性启动子具有定位良好的+1 和-1 核小体,与周期性的 10 个碱基 WW 信号(W = A/T)相关。体细胞特异性启动子缺乏定位核小体和这个信号,具有广泛的核小体缺失区域,并且富含核心启动子元件,这些元件在不同组织之间有很大的差异。我们在其他动物的普遍存在的启动子中观察到 10 个碱基周期性的 WW 信号,表明它是一种古老的保守信号。我们的研究结果表明生殖系和体细胞特异性基因的调控结构存在根本差异,揭示了产生不同基因表达模式的调控规则,并为未来的研究提供了一个组织特异性的资源。