Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
School of Software Technology, Dalian University of Technology, Dalian, China.
Nat Genet. 2022 Mar;54(3):295-305. doi: 10.1038/s41588-022-01026-x. Epub 2022 Mar 10.
The role of histone modifications in transcription remains incompletely understood. Here, we examine the relationship between histone modifications and transcription using experimental perturbations combined with sensitive machine-learning tools. Transcription predicted the variation in active histone marks and complex chromatin states, like bivalent promoters, down to single-nucleosome resolution and at an accuracy that rivaled the correspondence between independent ChIP-seq experiments. Blocking transcription rapidly removed two punctate marks, H3K4me3 and H3K27ac, from chromatin indicating that transcription is required for active histone modifications. Transcription was also required for maintenance of H3K27me3, consistent with a role for RNA in recruiting PRC2. A subset of DNase-I-hypersensitive sites were refractory to prediction, precluding models where transcription initiates pervasively at any open chromatin. Our results, in combination with past literature, support a model in which active histone modifications serve a supportive, rather than an essential regulatory, role in transcription.
组蛋白修饰在转录中的作用仍不完全清楚。在这里，我们使用实验扰动结合敏感的机器学习工具来研究组蛋白修饰和转录之间的关系。转录可以预测活性组蛋白标记和复杂染色质状态（如二价启动子）的变化，其分辨率可达到单个核小体，并且准确性可与独立的 ChIP-seq 实验相媲美。阻断转录会迅速将两个点状标记 H3K4me3 和 H3K27ac 从染色质中去除，表明转录是活性组蛋白修饰所必需的。转录对于 H3K27me3 的维持也是必需的，这与 RNA 在招募 PRC2 中的作用一致。一小部分 DNase-I 超敏位点无法预测，这排除了转录在任何开放染色质中普遍起始的模型。我们的结果与过去的文献相结合，支持这样一种模型，即活性组蛋白修饰在转录中起支持而非必需的调控作用。
