• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

DROSHA在维持哺乳动物CpG甲基化中的新作用。

A novel requirement for DROSHA in maintenance of mammalian CG methylation.

作者信息

Stathopoulou Athanasia, Chhetri Jyoti B, Ambrose John C, Estève Pierre-Olivier, Ji Lexiang, Erdjument-Bromage Hediye, Zhang Guoqiang, Neubert Thomas A, Pradhan Sriharsa, Herrero Javier, Schmitz Robert J, Ooi Steen K T

机构信息

Department of Cancer Biology, UCL Cancer Institute, London WC1E 6BT, UK.

Bill Lyons Informatics Centre, UCL Cancer Institute, London WC1E 6BT, UK.

出版信息

Nucleic Acids Res. 2017 Sep 19;45(16):9398-9412. doi: 10.1093/nar/gkx695.

DOI:10.1093/nar/gkx695
PMID:28934503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5766157/
Abstract

In mammals, faithful inheritance of genomic methylation patterns ensures proper gene regulation and cell behaviour, impacting normal development and fertility. Following establishment, genomic methylation patterns are transmitted through S-phase by the maintenance methyltransferase Dnmt1. Using a protein interaction screen, we identify Microprocessor component DROSHA as a novel DNMT1-interactor. Drosha-deficient embryonic stem (ES) cells display genomic hypomethylation that is not accounted for by changes in the levels of DNMT proteins. DNMT1-mediated methyltransferase activity is also reduced in these cells. We identify two transcripts that are specifically upregulated in Drosha- but not Dicer-deficient ES cells. Regions within these transcripts predicted to form stem-loop structures are processed by Microprocessor and can inhibit DNMT1-mediated methylation in vitro. Our results highlight DROSHA as a novel regulator of mammalian DNA methylation and we propose that DROSHA-mediated processing of RNA is necessary to ensure full DNMT1 activity. This adds to the DROSHA repertoire of non-miRNA dependent functions as well as implicating RNA in regulating DNMT1 activity and correct levels of genomic methylation.

摘要

在哺乳动物中，基因组甲基化模式的忠实遗传确保了适当的基因调控和细胞行为，影响正常发育和生育能力。建立之后，基因组甲基化模式通过维持甲基转移酶Dnmt1在S期进行传递。通过蛋白质相互作用筛选，我们鉴定出微处理器组件DROSHA是一种新型的DNMT1相互作用蛋白。缺乏Drosha的胚胎干细胞（ES细胞）表现出基因组低甲基化，这不能用DNMT蛋白水平的变化来解释。这些细胞中DNMT1介导的甲基转移酶活性也降低。我们鉴定出两种在缺乏Drosha而非缺乏Dicer的ES细胞中特异性上调的转录本。这些转录本中预测形成茎环结构的区域由微处理器加工处理，并且在体外能够抑制DNMT1介导的甲基化。我们的结果突出了DROSHA作为哺乳动物DNA甲基化的新型调节因子，并且我们提出DROSHA介导的RNA加工对于确保完整的DNMT1活性是必要的。这增加了DROSHA非依赖于miRNA的功能种类，同时也表明RNA在调节DNMT1活性和正确的基因组甲基化水平中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/e781d5dbf62b/gkx695fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/dc8b159221d7/gkx695fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/b0d624b4d6ff/gkx695fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/d860427bf10c/gkx695fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/e90672352916/gkx695fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/e781d5dbf62b/gkx695fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/dc8b159221d7/gkx695fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/b0d624b4d6ff/gkx695fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/d860427bf10c/gkx695fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/e90672352916/gkx695fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b56/5766157/e781d5dbf62b/gkx695fig5.jpg

相似文献

1
A novel requirement for DROSHA in maintenance of mammalian CG methylation.DROSHA在维持哺乳动物CpG甲基化中的新作用。
Nucleic Acids Res. 2017 Sep 19;45(16):9398-9412. doi: 10.1093/nar/gkx695.
2
Distinct roles of DNMT1-dependent and DNMT1-independent methylation patterns in the genome of mouse embryonic stem cells.DNA甲基转移酶1（DNMT1）依赖性和非DNMT1依赖性甲基化模式在小鼠胚胎干细胞基因组中的不同作用。
Genome Biol. 2015 Jun 2;16(1):115. doi: 10.1186/s13059-015-0685-2.
3
Normal DNA methylation dynamics in DICER1-deficient mouse embryonic stem cells.DICER1 缺陷型小鼠胚胎干细胞中的正常 DNA 甲基化动态。
PLoS Genet. 2012 Sep;8(9):e1002919. doi: 10.1371/journal.pgen.1002919. Epub 2012 Sep 6.
4
DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta.DNA 甲基化介导的 DNA 甲基转移酶-1（DNMT1）下调与人类胎盘的全基因组低甲基化同时发生，但不是必需的。
J Biol Chem. 2010 Mar 26;285(13):9583-9593. doi: 10.1074/jbc.M109.064956. Epub 2010 Jan 13.
5
Identification of a region of the DNMT1 methyltransferase that regulates the maintenance of genomic imprints.鉴定调控基因组印迹维持的 DNMT1 甲基转移酶区域。
Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20806-11. doi: 10.1073/pnas.0905668106. Epub 2009 Nov 18.
6
CFP1 interacts with DNMT1 independently of association with the Setd1 Histone H3K4 methyltransferase complexes.CFP1与DNMT1相互作用，且这种相互作用独立于与Setd1组蛋白H3K4甲基转移酶复合物的关联。
DNA Cell Biol. 2008 Oct;27(10):533-43. doi: 10.1089/dna.2007.0714.
7
DNA Methyltransferase protein synthesis is reduced in CXXC finger protein 1-deficient embryonic stem cells.在CXXC指蛋白1缺陷的胚胎干细胞中，DNA甲基转移酶的蛋白质合成减少。
DNA Cell Biol. 2009 May;28(5):223-31. doi: 10.1089/dna.2009.0854.
8
UHRF1 plays a role in maintaining DNA methylation in mammalian cells.UHRF1在维持哺乳动物细胞中的DNA甲基化方面发挥作用。
Science. 2007 Sep 21;317(5845):1760-4. doi: 10.1126/science.1147939. Epub 2007 Aug 2.
9
Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.通过SET7介导的赖氨酸甲基化调控哺乳动物细胞中DNMT1的稳定性
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5076-81. doi: 10.1073/pnas.0810362106. Epub 2009 Mar 12.
10
Mammalian cytosine DNA methyltransferase Dnmt1: enzymatic mechanism, novel mechanism-based inhibitors, and RNA-directed DNA methylation.哺乳动物胞嘧啶DNA甲基转移酶Dnmt1：酶促机制、新型基于机制的抑制剂以及RNA指导的DNA甲基化
Curr Med Chem. 2008;15(1):92-106. doi: 10.2174/092986708783330700.

引用本文的文献

1
RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.RXR 激动剂增强来那度胺的抗骨髓瘤活性和 T 细胞功能，同时保留降血糖作用。
Cells. 2023 Aug 3;12(15):1993. doi: 10.3390/cells12151993.
2
The Mutagenic Consequences of DNA Methylation within and across Generations.DNA甲基化在代内和代际间的诱变后果。
Epigenomes. 2022 Oct 4;6(4):33. doi: 10.3390/epigenomes6040033.
3
An Epigenetic Role of Mitochondria in Cancer.线粒体在癌症中的表观遗传学作用。

本文引用的文献

1
DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells.无催化活性的 DNMT3B 异构体作为辅助蛋白在体细胞中刺激基因体甲基化。
Nat Commun. 2016 Apr 28;7:11453. doi: 10.1038/ncomms11453.
2
Role of TET enzymes in DNA methylation, development, and cancer.TET 酶在 DNA 甲基化、发育及癌症中的作用。
Genes Dev. 2016 Apr 1;30(7):733-50. doi: 10.1101/gad.276568.115.
3
Drosha controls dendritic cell development by cleaving messenger RNAs encoding inhibitors of myelopoiesis.Drosha 通过切割编码髓系抑制物的信使 RNA 来控制树突状细胞的发育。
Cells. 2022 Aug 13;11(16):2518. doi: 10.3390/cells11162518.
4
PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.PPAR 激动剂可减弱来那度胺在体外和体内的抗骨髓瘤活性。
Cancer Lett. 2022 Oct 1;545:215832. doi: 10.1016/j.canlet.2022.215832. Epub 2022 Jul 22.
5
The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection.宿主细胞 DNA 甲基化在细菌感染免疫反应中的作用。
Front Immunol. 2021 Jul 29;12:696280. doi: 10.3389/fimmu.2021.696280. eCollection 2021.
6
Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors.宿主微小RNA特性及其与表观遗传学、长链非编码RNA和异种感染因子的关联概述。
Cell Biosci. 2021 Feb 25;11(1):43. doi: 10.1186/s13578-021-00552-1.
7
Epigenetic dynamics in cancer stem cell dormancy.癌症干细胞休眠中的表观遗传动态。
Cancer Metastasis Rev. 2020 Sep;39(3):721-738. doi: 10.1007/s10555-020-09882-x.
8
Mechanisms of DNA Methyltransferase Recruitment in Mammals.哺乳动物中DNA甲基转移酶招募的机制。
Genes (Basel). 2018 Dec 10;9(12):617. doi: 10.3390/genes9120617.
Nat Immunol. 2015 Nov;16(11):1134-41. doi: 10.1038/ni.3293. Epub 2015 Oct 5.
4
Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation.染色体。一个全面的Xist相互作用组揭示了黏连蛋白排斥作用和一种RNA导向的染色体构象。
Science. 2015 Jul 17;349(6245). doi: 10.1126/science.aab2276. Epub 2015 Jun 18.
5
The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis.Dnmt3L的ADD结构域在精子发生过程中控制胞嘧啶甲基化的建立。
Cell Rep. 2015 Feb 17;10(6):944-956. doi: 10.1016/j.celrep.2015.01.021. Epub 2015 Feb 13.
6
DNMT1-interacting RNAs block gene-specific DNA methylation.DNMT1 相互作用 RNA 阻断基因特异性 DNA 甲基化。
Nature. 2013 Nov 21;503(7476):371-6. doi: 10.1038/nature12598. Epub 2013 Oct 9.
7
FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency.FGF 信号抑制可促使胚胎干细胞快速进行全基因组去甲基化，达到多能性的表观遗传基础状态。
Cell Stem Cell. 2013 Sep 5;13(3):351-9. doi: 10.1016/j.stem.2013.06.004. Epub 2013 Jul 11.
8
Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells.对小鼠胚胎干细胞中两种不同可相互转化的 DNA 甲基化组进行全基因组亚硫酸氢盐测序。
Cell Stem Cell. 2013 Sep 5;13(3):360-9. doi: 10.1016/j.stem.2013.06.002. Epub 2013 Jul 11.
9
Naive pluripotency is associated with global DNA hypomethylation.原始的多能性与全球 DNA 低甲基化有关。
Nat Struct Mol Biol. 2013 Mar;20(3):311-6. doi: 10.1038/nsmb.2510. Epub 2013 Feb 17.
10
RNA-guided human genome engineering via Cas9.通过 Cas9 进行 RNA 引导的人类基因组工程。
Science. 2013 Feb 15;339(6121):823-6. doi: 10.1126/science.1232033. Epub 2013 Jan 3.