Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications
Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications
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DOI：
10.1016/j.celrep.2019.06.097
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发表时间：
2019-07-30
期刊：
影响因子：
8.8
通讯作者：
Robert, Francois
中科院分区：
文献类型：
--
作者：
Jeronimo, Celia;Poitras, Christian;Robert, Francois
基因组DNA由额外的信息层构成，称为表观基因组。表观基因组标记，如DNA甲基化、组蛋白修饰和组蛋白变体，集中在特定的基因组位置，在那里它们可以指示和反映基因的表达。这些信息是如何保持的，尤其是在转录的情况下，还没有完全被理解。具体地说，通过RNA聚合酶II传递的修饰的组蛋白本身的保留程度尚不清楚。在这里，我们证明了当转录偶联的组蛋白伴侣蛋白FACT或Spt6在酿酒酵母中被破坏时，几个组蛋白修饰被错位定位。在没有功能因子或Spt6的情况下，转录会产生核小体丢失，这可以通过非转录偶联的组蛋白伴侣蛋白活性的增加来部分补偿。被转录驱逐的修饰组蛋白的随机掺入扰乱了表观基因组信息。我们的工作强调了在转录过程中通过FACT和Spt6局部循环修饰的组蛋白在维持表观基因组图谱中的重要性。
Genomic DNA is framed by additional layers of information, referred to as the epigenome. Epigenomic marks such as DNA methylation, histone modifications, and histone variants are concentrated on specific genomic sites, where they can both instruct and reflect gene expression. How this information is maintained, notably in the face of transcription, is not completely understood. Specifically, the extent to which modified histones themselves are retained through RNA polymerase II passage is unclear. Here, we show that several histone modifications are mislocalized when the transcription-coupled histone chaperones FACT or Spt6 are disrupted in Saccharomyces cerevisiae. In the absence of functional FACT or Spt6, transcription generates nucleosome loss, which is partially compensated for by the increased activity of non-transcription-coupled histone chaperones. The random incorporation of transcription-evicted modified histones scrambles epigenomic information. Our work highlights the importance of local recycling of modified histones by FACT and Spt6 during transcription in the maintenance of the epigenomic landscape.