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新生转录数据实现组蛋白翻译后修饰模式的预测
作者:小柯机器人 发布时间:2022/3/13 17:38:33

美国康奈尔大学Charles G. Danko研究组利用新生转录数据实现组蛋白翻译后修饰模式的预测。2022年3月10日,国际知名学术期刊《自然—遗传学》在线发表了这一成果。

使用实验扰动与敏感的机器学习工具相结合,研究人员揭示了组蛋白修饰和转录之间的关系。转录预测了活跃的组蛋白标记和复杂的染色质状态的变化,如二价启动子,其准确度可与独立的ChIP-seq实验之间的对应关系相媲美,达到了单核小体分辨率。阻断转录可迅速从染色质中去除两个点状标记,即H3K4me3和H3K27ac,表明转录是活跃组蛋白修饰所必需的。

转录也是维持H3K27me3的必要条件,这与RNA招募PRC2的作用一致。一组对DNase-I不敏感的位点难以预测,排除了转录在任何开放染色质中普遍启动的模型。这些结果,并结合过去的文献,支持一种模型:活跃的组蛋白修饰在转录中起着支持性的作用,而不是基本的调节作用。

据悉,组蛋白修饰在转录中的作用仍然没有得到完全的理解。

附:英文原文

Title: Prediction of histone post-translational modification patterns based on nascent transcription data

Author: Wang, Zhong, Chivu, Alexandra G., Choate, Lauren A., Rice, Edward J., Miller, Donald C., Chu, Tinyi, Chou, Shao-Pei, Kingsley, Nicole B., Petersen, Jessica L., Finno, Carrie J., Bellone, Rebecca R., Antczak, Douglas F., Lis, John T., Danko, Charles G.

Issue&Volume: 2022-03-10

Abstract: 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. A machine-learning tool can predict the distribution of histone post-translational modifications using nascent transcription data. Inhibiting transcription impacts H3K4me3, H3K27ac and H3K27me3 dynamics.

DOI: 10.1038/s41588-022-01026-x

Source: https://www.nature.com/articles/s41588-022-01026-x

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex