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组蛋白去甲基化酶协调维持 H3K36/K27 甲基化,维持生殖细胞的身份和永生。

Coordinated maintenance of H3K36/K27 methylation by histone demethylases preserves germ cell identity and immortality.

机构信息

Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes vej 5, Copenhagen DK-2200, Denmark.

Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy.

出版信息

Cell Rep. 2021 Nov 23;37(8):110050. doi: 10.1016/j.celrep.2021.110050.

Abstract

Germ cells have evolved unique mechanisms to ensure the transmission of genetically and nongenetically encoded information, whose alteration compromises germ cell immortality. Chromatin factors play fundamental roles in these mechanisms. H3K36 and H3K27 methyltransferases shape and propagate a pattern of histone methylation essential for C. elegans germ cell maintenance, but the role of respective histone demethylases remains unexplored. Here, we show that jmjd-5 regulates H3K36me2 and H3K27me3 levels, preserves germline immortality, and protects germ cell identity by controlling gene expression. The transcriptional and biological effects of jmjd-5 loss can be hindered by the removal of H3K27demethylases, indicating that H3K36/K27 demethylases act in a transcriptional framework and promote the balance between H3K36 and H3K27 methylation required for germ cell immortality. Furthermore, we find that in wild-type, but not in jmjd-5 mutants, alterations of H3K36 methylation and transcription occur at high temperature, suggesting a role for jmjd-5 in adaptation to environmental changes.

摘要

生殖细胞进化出了独特的机制来确保遗传和非遗传信息的传递,这些信息的改变会损害生殖细胞的永生性。染色质因子在这些机制中起着至关重要的作用。H3K36 和 H3K27 甲基转移酶塑造并传播了一种组蛋白甲基化模式,这种模式对于线虫生殖细胞的维持至关重要,但各自的组蛋白去甲基酶的作用仍未被探索。在这里,我们表明 jmjd-5 通过控制基因表达来调节 H3K36me2 和 H3K27me3 水平,保持生殖系永生,并保护生殖细胞身份。jmjd-5 缺失的转录和生物学效应可以通过去除 H3K27 去甲基酶来阻止,这表明 H3K36/K27 去甲基酶在转录框架中起作用,并促进生殖细胞永生所需的 H3K36 和 H3K27 甲基化之间的平衡。此外,我们发现,在野生型中,但不在 jmjd-5 突变体中,H3K36 甲基化和转录的改变会在高温下发生,这表明 jmjd-5 在适应环境变化方面发挥了作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c4/8640224/3892c53ba7f7/fx1.jpg

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