丹麦哥本哈根大学Kristian Helin研究团队利用组蛋白编辑阐明哺乳动物中H3K27甲基化和乙酰化的功能作用。2022年6月6日,《自然—遗传学》杂志在线发表了这项成果。
Author: Sankar, Aditya, Mohammad, Faizaan, Sundaramurthy, Arun Kumar, Wang, Hua, Lerdrup, Mads, Tatar, Tulin, Helin, Kristian
Issue&Volume: 2022-06-06
Abstract: Posttranslational modifications of histones (PTMs) are associated with specific chromatin and gene expression states1,2. Although studies in Drosophila melanogaster have revealed phenotypic associations between chromatin-modifying enzymes and their histone substrates, comparable studies in mammalian models do not exist3,4,5. Here, we use CRISPR base editing in mouse embryonic stem cells (mESCs) to address the regulatory role of lysine 27 of histone H3 (H3K27), a substrate for Polycomb repressive complex 2 (PRC2)-mediated methylation and CBP/EP300-mediated acetylation6,7. By generating pan-H3K27R (pK27R) mutant mESCs, where all 28 alleles of H3.1, H3.2 and H3.3 have been mutated, we demonstrate similarity in transcription patterns of genes and differentiation to PRC2-null mutants. Moreover, H3K27 acetylation is not essential for gene derepression linked to loss of H3K27 methylation, or de novo activation of genes during cell-fate transition to epiblast-like cells (EpiLCs). In conclusion, our results show that H3K27 is an essential substrate for PRC2 in mESCs, whereas other PTMs in addition to H3K27 acetylation are likely involved in mediating CBP/EP300 function. Our work demonstrates the feasibility of large-scale multicopy gene editing to interrogate histone PTM function in mammalian cells.
DOI: 10.1038/s41588-022-01091-2
Source: https://www.nature.com/articles/s41588-022-01091-2
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