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H3K4 甲基化在转录调控中的功能作用。

Functional Roles of H3K4 Methylation in Transcriptional Regulation.

机构信息

Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.

Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.

出版信息

Mol Cell Biol. 2024;44(11):505-515. doi: 10.1080/10985549.2024.2388254. Epub 2024 Aug 18.

DOI:10.1080/10985549.2024.2388254
PMID:39155435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11529435/
Abstract

Histone 3 lysine 4 methylation (H3K4me) is a highly evolutionary conserved chromatin modification associated with active transcription, and its three methylation states-mono, di, and trimethylation-mark distinct regulatory elements. However, whether H3K4me plays functional roles in transcriptional regulation or is merely a by-product of histone methyltransferases recruited to actively transcribed loci is still under debate. Here, we outline the studies that have addressed this question in yeast, , and mammalian systems. We review evidence from histone residue mutation, histone modifier manipulation, and epigenetic editing, focusing on the relative roles of H3K4me1 and H3K4me3. We conclude that H3K4me1 and H3K4me3 may have convergent functions in establishing open chromatin and promoting transcriptional activation during cell differentiation.

摘要

组蛋白 3 赖氨酸 4 甲基化(H3K4me)是一种高度进化保守的染色质修饰,与活跃的转录相关联,其三种甲基化状态——单甲基化、二甲基化和三甲基化——标记着不同的调控元件。然而,H3K4me 是否在转录调控中发挥功能作用,还是仅仅是招募到活跃转录基因座的组蛋白甲基转移酶的副产物,仍存在争议。在这里,我们概述了在酵母、 和哺乳动物系统中解决这个问题的研究。我们回顾了组蛋白残基突变、组蛋白修饰因子操作和表观遗传编辑的证据,重点关注 H3K4me1 和 H3K4me3 的相对作用。我们的结论是,H3K4me1 和 H3K4me3 可能在细胞分化过程中建立开放染色质和促进转录激活方面具有趋同功能。

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Nat Genet. 2024 Jun;56(6):1168-1180. doi: 10.1038/s41588-024-01706-w. Epub 2024 May 9.
2
Set7 Methyltransferase and Phenotypic Switch in Diabetic Glomerular Endothelial Cells.Set7 甲基转移酶与糖尿病肾小球内皮细胞表型转换。
J Am Soc Nephrol. 2024 Jun 1;35(6):733-748. doi: 10.1681/ASN.0000000000000345. Epub 2024 Apr 17.
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Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition.LSD1 在调控增强子和细胞命运转变中的去甲基酶非依赖性作用。
Nat Commun. 2023 Aug 22;14(1):4944. doi: 10.1038/s41467-023-40606-1.
4
MLL3/MLL4 methyltransferase activities control early embryonic development and embryonic stem cell differentiation in a lineage-selective manner.MLL3/MLL4 甲基转移酶活性以谱系选择性方式控制早期胚胎发育和胚胎干细胞分化。
Nat Genet. 2023 Apr;55(4):693-705. doi: 10.1038/s41588-023-01356-4. Epub 2023 Apr 3.
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H3K4me2/3 modulate the stability of RNA polymerase II pausing.H3K4me2/3调节RNA聚合酶II暂停的稳定性。
Cell Res. 2023 May;33(5):403-406. doi: 10.1038/s41422-023-00794-3. Epub 2023 Mar 15.
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