• 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

Menin 敲低会影响干扰素-γ诱导的 IRF1 基因的前体 mRNA 加工和启动子保真度。

Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene.

机构信息

Department of Biology, The University of Virginia, 485 McCormick Road, Charlottesville, VA 22903, USA.

出版信息

Epigenetics Chromatin. 2012 Jan 12;5(1):2. doi: 10.1186/1756-8935-5-2.

DOI:10.1186/1756-8935-5-2
PMID:22240255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3271985/
Abstract

BACKGROUND

The tumor suppressor menin (MEN1) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (IRF1), and is further recruited when IRF1 transcription is triggered by interferon-γ signaling.

RESULTS

RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at IRF1. While MEN1 knockdown does not impact the rate of transcription, IRF1 heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the IRF1 promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with IRF1, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.

CONCLUSIONS

Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.

摘要

背景

肿瘤抑制因子 menin（MEN1）在遗传性疾病多发性内分泌肿瘤 I 型中发生突变，具有几个已记录的细胞作用，包括几种转录因子激活和抑制转录。作为激活剂，MEN1 是 Set1 样混合谱系白血病（MLL）MLL1/MLL2 甲基转移酶复合物的组成部分，该复合物甲基化组蛋白 H3 赖氨酸 4（H3K4）。MEN1 定位于信号转导和转录激活因子 1（STAT1）依赖性基因干扰素调节因子 1（IRF1），当干扰素-γ信号触发 IRF1 转录时，进一步募集。

结果

RNAi 介导的 MEN1 敲低改变了 H3K4 二甲基化和 H3 乙酰化谱，以及组蛋白去乙酰化酶 3 在 IRF1 中的定位。虽然 MEN1 敲低不影响转录率，但 IRF1 异核转录物在 MEN1 耗尽的细胞中富集。加工的 mRNA 和翻译的蛋白产物同时减少，抗病毒状态减弱。此外，IRF1 启动子处的转录起始位点在 MEN1 耗尽的细胞中被破坏。H3K4 去甲基酶赖氨酸特异性去甲基酶 1 也与 IRF1 相关，其抑制改变了 H3K4 甲基化并破坏了转录起始位点。

结论

总之，数据表明 MEN1 以一种新的方式促进 STAT1 激活的基因表达，包括定义转录起始位点和 RNA 加工。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/36e8971ef8c0/1756-8935-5-2-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/da4c2c2886fa/1756-8935-5-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/c8c6d70af492/1756-8935-5-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/1e741ff8eea5/1756-8935-5-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/be00d1ffee28/1756-8935-5-2-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/259925e0e933/1756-8935-5-2-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/7ed98c9cb80f/1756-8935-5-2-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/36e8971ef8c0/1756-8935-5-2-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/da4c2c2886fa/1756-8935-5-2-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/c8c6d70af492/1756-8935-5-2-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/1e741ff8eea5/1756-8935-5-2-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/be00d1ffee28/1756-8935-5-2-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/259925e0e933/1756-8935-5-2-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/7ed98c9cb80f/1756-8935-5-2-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/3271985/36e8971ef8c0/1756-8935-5-2-7.jpg

相似文献

1
Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene.Menin 敲低会影响干扰素-γ诱导的 IRF1 基因的前体 mRNA 加工和启动子保真度。
Epigenetics Chromatin. 2012 Jan 12;5(1):2. doi: 10.1186/1756-8935-5-2.
2
Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1)-activated transcription of the interferon regulatory factor 1 gene (IRF1).Menin 和 RNF20 的募集与动态组蛋白修饰有关，这些修饰调节信号转导子和转录激活子 1（STAT1）激活的干扰素调节因子 1 基因（IRF1）转录。
Epigenetics Chromatin. 2010 Sep 8;3(1):16. doi: 10.1186/1756-8935-3-16.
3
Multi-omics analyses of MEN1 missense mutations identify disruption of menin-MLL and menin-JunD interactions as critical requirements for molecular pathogenicity.MEN1 错义突变的多组学分析确定了 menin-MLL 和 menin-JunD 相互作用的破坏是分子发病机制的关键要求。
Epigenetics Chromatin. 2022 Aug 9;15(1):29. doi: 10.1186/s13072-022-00461-8.
4
The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates peroxisome proliferator-activated receptor gamma-dependent adipocyte differentiation.多发性内分泌腺瘤1型（MEN1）肿瘤抑制因子调节过氧化物酶体增殖物激活受体γ依赖性脂肪细胞分化。
Mol Cell Biol. 2009 Sep;29(18):5060-9. doi: 10.1128/MCB.01001-08. Epub 2009 Jul 13.
5
Dynamic epigenetic regulation by menin during pancreatic islet tumor formation.在胰岛肿瘤形成过程中，Menin对表观遗传的动态调控
Mol Cancer Res. 2015 Apr;13(4):689-98. doi: 10.1158/1541-7786.MCR-14-0457. Epub 2014 Dec 23.
6
Menin links estrogen receptor activation to histone H3K4 trimethylation.Menin将雌激素受体激活与组蛋白H3K4三甲基化联系起来。
Cancer Res. 2006 May 1;66(9):4929-35. doi: 10.1158/0008-5472.CAN-05-4461.
7
Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1.二十年来的 MENIN： MEN1 转录调控恢复的新机遇。
Endocr Relat Cancer. 2017 Oct;24(10):T135-T145. doi: 10.1530/ERC-17-0281. Epub 2017 Aug 15.
8
A novel disrupter of telomere silencing 1-like (DOT1L) interaction is required for signal transducer and activator of transcription 1 (STAT1)-activated gene expression.一种新型端粒沉默 1 样（DOT1L）相互作用破坏剂可用于信号转导和转录激活因子 1（STAT1）激活的基因表达。
J Biol Chem. 2011 Dec 2;286(48):41195-41204. doi: 10.1074/jbc.M111.284190. Epub 2011 Oct 15.
9
Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation.疾病机制：1型多发性内分泌肿瘤与染色质修饰及转录调控的关系
Nat Clin Pract Endocrinol Metab. 2006 Oct;2(10):562-70. doi: 10.1038/ncpendmet0292.
10
The same pocket in menin binds both MLL and JUND but has opposite effects on transcription.在男性中，同一个口袋结合了 MLL 和 JUND，但对转录有相反的影响。
Nature. 2012 Feb 12;482(7386):542-6. doi: 10.1038/nature10806.

引用本文的文献

1
STING nuclear partners contribute to innate immune signaling responses.干扰素基因刺激蛋白（STING）的核伴侣有助于先天性免疫信号反应。
iScience. 2021 Aug 28;24(9):103055. doi: 10.1016/j.isci.2021.103055. eCollection 2021 Sep 24.
2
Hijacked in cancer: the KMT2 (MLL) family of methyltransferases.癌症中的“劫持者”：KMT2（MLL）甲基转移酶家族
Nat Rev Cancer. 2015 Jun;15(6):334-46. doi: 10.1038/nrc3929.

本文引用的文献

1
Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements.动态组蛋白乙酰化对于共转录剪接体组装和剪接体重排至关重要。
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2004-9. doi: 10.1073/pnas.1011982108. Epub 2011 Jan 18.
2
Epigenetics in alternative pre-mRNA splicing.表观遗传学在可变剪接中的作用。
Cell. 2011 Jan 7;144(1):16-26. doi: 10.1016/j.cell.2010.11.056.
3
Cross-talk in transcription, splicing and chromatin: who makes the first call?转录、剪接和染色质的串扰：谁先打第一通电话？
Biochem Soc Trans. 2010 Oct;38(5):1251-6. doi: 10.1042/BST0381251.
4
Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1)-activated transcription of the interferon regulatory factor 1 gene (IRF1).Menin 和 RNF20 的募集与动态组蛋白修饰有关，这些修饰调节信号转导子和转录激活子 1（STAT1）激活的干扰素调节因子 1 基因（IRF1）转录。
Epigenetics Chromatin. 2010 Sep 8;3(1):16. doi: 10.1186/1756-8935-3-16.
5
Chromatin immunoprecipitation (ChIP) to assay dynamic histone modification in activated gene expression in human cells.染色质免疫沉淀法（ChIP）用于检测人类细胞中激活基因表达过程中的动态组蛋白修饰。
J Vis Exp. 2010 Jul 29(41):2053. doi: 10.3791/2053.
6
Menin dynamics and functional insight: take your partners.Menin 动态及其功能见解：带上你的伴侣。
Mol Cell Endocrinol. 2010 Sep 15;326(1-2):80-4. doi: 10.1016/j.mce.2010.04.011. Epub 2010 Apr 24.
7
MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele.MLL-AF9 诱导的白血病发生需要野生型 Mll 等位基因的共表达。
Cancer Cell. 2010 Feb 17;17(2):148-59. doi: 10.1016/j.ccr.2009.12.034.
8
Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas.MEN1相关甲状旁腺腺瘤中维生素D受体功能的调节
Mol Cell Endocrinol. 2009 Dec 10;313(1-2):1-8. doi: 10.1016/j.mce.2009.08.020. Epub 2009 Sep 1.
9
Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II.H3K4甲基化的全基因组分析确定了MLL家族成员的靶点，并指出MLL1介导的H3K4甲基化在RNA聚合酶II调控转录起始过程中的作用。
Mol Cell Biol. 2009 Nov;29(22):6074-85. doi: 10.1128/MCB.00924-09. Epub 2009 Aug 24.
10
Histone H3 lysine 4 di-methylation: a novel mark for transcriptional fidelity?组蛋白H3赖氨酸4二甲基化：转录保真度的新标记？
Epigenetics. 2009 Jul 1;4(5):302-6. doi: 10.4161/epi.4.5.9369. Epub 2009 Jul 25.