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富含GT的启动子可驱动非洲锥虫中RNA聚合酶II的转录以及H2A.Z的沉积。

GT-rich promoters can drive RNA pol II transcription and deposition of H2A.Z in African trypanosomes.

作者信息

Wedel Carolin, Förstner Konrad U, Derr Ramona, Siegel T Nicolai

机构信息

Research Center for Infectious Diseases, Universität Würzburg, Würzburg, Germany.

Core Unit Systems Medicine, Universität Würzburg, Würzburg, Germany.

出版信息

EMBO J. 2017 Sep 1;36(17):2581-2594. doi: 10.15252/embj.201695323. Epub 2017 Jul 12.

DOI:10.15252/embj.201695323
PMID:28701485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5579346/
Abstract

Genome-wide transcription studies are revealing an increasing number of "dispersed promoters" that, unlike "focused promoters", lack well-conserved sequence motifs and tight regulation. Dispersed promoters are nevertheless marked by well-defined chromatin structures, suggesting that specific sequence elements must exist in these unregulated promoters. Here, we have analyzed regions of transcription initiation in the eukaryotic parasite in which RNA polymerase II transcription initiation occurs over broad regions without distinct promoter motifs and lacks regulation. Using a combination of site-specific and genome-wide assays, we identified GT-rich promoters that can drive transcription and promote the targeted deposition of the histone variant H2A.Z in a genomic context-dependent manner. In addition, upon mapping nucleosome occupancy at high resolution, we find nucleosome positioning to correlate with RNA pol II enrichment and gene expression, pointing to a role in RNA maturation. Nucleosome positioning may thus represent a previously unrecognized layer of gene regulation in trypanosomes. Our findings show that even highly dispersed, unregulated promoters contain specific DNA elements that are able to induce transcription and changes in chromatin structure.

摘要

全基因组转录研究揭示出越来越多的“分散启动子”，与“聚焦启动子”不同，它们缺乏保守的序列基序和严格的调控。然而，分散启动子具有明确的染色质结构，这表明这些不受调控的启动子中必定存在特定的序列元件。在此，我们分析了真核寄生虫中的转录起始区域，其中RNA聚合酶II转录起始发生在广泛区域，没有明显的启动子基序且缺乏调控。通过结合位点特异性和全基因组分析方法，我们鉴定出富含GT的启动子，它们能够驱动转录并以基因组背景依赖的方式促进组蛋白变体H2A.Z的靶向沉积。此外，在高分辨率绘制核小体占据情况时，我们发现核小体定位与RNA聚合酶II富集和基因表达相关，表明其在RNA成熟中发挥作用。因此，核小体定位可能代表了锥虫中以前未被认识的基因调控层面。我们的研究结果表明，即使是高度分散、不受调控的启动子也包含能够诱导转录和染色质结构变化的特定DNA元件。

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