• 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

HDAC1/2/3是对启动子去琥珀酰化至关重要的主要组蛋白去琥珀酰化酶。

HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation.

作者信息

Li Jialun, Lu Lu, Liu Lingling, Ren Xuelian, Chen Jiwei, Yin Xingzhi, Xiao Yanhui, Li Jiwen, Wei Gang, Huang He, Wei Wei, Wong Jiemin

机构信息

Wuhu Hospital, East China Normal University, Wuhu, Anhui, China.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

出版信息

Cell Discov. 2023 Aug 15;9(1):85. doi: 10.1038/s41421-023-00573-9.

DOI:10.1038/s41421-023-00573-9
PMID:37580347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/
Abstract

Lysine succinylation is one of the major post-translational modifications occurring on histones and is believed to have significant roles in regulating chromatin structure and function. Currently, histone desuccinylation is widely believed to be catalyzed by members of the SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in a marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, our integrated analysis revealed that promoter histone succinylation positively correlates with gene transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation.

摘要

赖氨酸琥珀酰化是发生在组蛋白上的主要翻译后修饰之一，并且被认为在调节染色质结构和功能中具有重要作用。目前，人们普遍认为组蛋白去琥珀酰化是由SIRT家族去乙酰化酶成员催化的。在此，我们报告组蛋白去琥珀酰化实际上主要是由I类HDAC1/2/3催化的。抑制或缺失HDAC1/2/3会导致整体组蛋白琥珀酰化显著增加，而异位表达HDAC1/2/3而非其无去乙酰化酶活性的突变体则会下调整体组蛋白琥珀酰化。我们证明I类HDAC1/2/3复合物在体外具有强大的组蛋白去琥珀酰化酶活性。基因组图谱分析显示，组蛋白琥珀酰化在基因启动子处高度富集，抑制HDAC活性会导致启动子组蛋白琥珀酰化显著升高。此外，我们的综合分析表明，启动子组蛋白琥珀酰化与基因转录活性呈正相关。总体而言，我们证明I类HDAC1/2/3而非SIRT家族蛋白是主要的组蛋白去琥珀酰化酶，对启动子组蛋白去琥珀酰化尤为重要。因此，我们的研究为组蛋白琥珀酰化在转录调控中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/b4dd07013940/41421_2023_573_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/3d369ae81fdf/41421_2023_573_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/5e844172eccd/41421_2023_573_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/02ed389653ba/41421_2023_573_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/31f332dda3d4/41421_2023_573_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/2f12ee8caa21/41421_2023_573_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/b4dd07013940/41421_2023_573_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/3d369ae81fdf/41421_2023_573_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/5e844172eccd/41421_2023_573_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/02ed389653ba/41421_2023_573_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/31f332dda3d4/41421_2023_573_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/2f12ee8caa21/41421_2023_573_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a7/10425439/b4dd07013940/41421_2023_573_Fig6_HTML.jpg

相似文献

1
HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation.HDAC1/2/3是对启动子去琥珀酰化至关重要的主要组蛋白去琥珀酰化酶。
Cell Discov. 2023 Aug 15;9(1):85. doi: 10.1038/s41421-023-00573-9.
2
Histone succinylation and its function on the nucleosome.组蛋白琥珀酰化及其在核小体上的功能。
J Cell Mol Med. 2021 Aug;25(15):7101-7109. doi: 10.1111/jcmm.16676. Epub 2021 Jun 23.
3
Succinylation modification: a potential therapeutic target in stroke.琥珀酰化修饰：中风的潜在治疗靶点
Neural Regen Res. 2024 Apr;19(4):781-787. doi: 10.4103/1673-5374.382229.
4
Quantitative analysis of histone deacetylase-1 selective histone modifications by differential mass spectrometry.通过差异质谱法对组蛋白去乙酰化酶-1选择性组蛋白修饰进行定量分析。
J Proteome Res. 2008 Dec;7(12):5177-86. doi: 10.1021/pr800510p.
5
Histone deacetylase inhibitors modulate the transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-a gene: interactive roles of modified histones, histone acetyltransferase, p300, AND Sp1.组蛋白去乙酰化酶抑制剂调节鸟苷酸环化酶/利钠肽受体-a 基因的转录调控：修饰组蛋白、组蛋白乙酰转移酶、p300 和 Sp1 的相互作用。
J Biol Chem. 2014 Mar 7;289(10):6991-7002. doi: 10.1074/jbc.M113.511444. Epub 2014 Jan 22.
6
Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides.解析组学揭示 Sirt5 催化组蛋白肽去琥珀酰化的分子机制。
Biochem J. 2019 Jan 18;476(2):211-223. doi: 10.1042/BCJ20180745.
7
Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.组蛋白去乙酰化酶（HDAC）1 和 2 复合物在体内调节组蛋白乙酰化和巴豆酰化。
Sci Rep. 2018 Oct 2;8(1):14690. doi: 10.1038/s41598-018-32927-9.
8
Histone deacetylase 1/mSin3A disrupts gamma interferon-induced CIITA function and major histocompatibility complex class II enhanceosome formation.组蛋白去乙酰化酶1/mSin3A破坏γ干扰素诱导的CIITA功能以及主要组织相容性复合体II类增强体的形成。
Mol Cell Biol. 2003 May;23(9):3091-102. doi: 10.1128/MCB.23.9.3091-3102.2003.
9
Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of Histone H3 Lysine 27 (H3K27) Deacetylation and Methylation.组蛋白去乙酰化酶1（HDAC1）通过协调组蛋白H3赖氨酸27（H3K27）的去乙酰化和甲基化来负向调节棕色脂肪细胞的产热程序。
J Biol Chem. 2016 Feb 26;291(9):4523-36. doi: 10.1074/jbc.M115.677930. Epub 2016 Jan 5.
10
SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities.组蛋白去乙酰化酶1（HDAC1）的小泛素样修饰物1（SUMO-1）修饰可调节其生物学活性。
J Biol Chem. 2002 Jun 28;277(26):23658-63. doi: 10.1074/jbc.M203690200. Epub 2002 Apr 17.

引用本文的文献

1
The function and mechanism of protein acylation in the regulation of viral infection.蛋白质酰化在病毒感染调控中的作用及机制。
Virulence. 2025 Dec;16(1):2530171. doi: 10.1080/21505594.2025.2530171. Epub 2025 Jul 17.
2
Acyl post-translational modification of proteins by metabolites in cancer cells.癌细胞中代谢物对蛋白质的酰基化翻译后修饰。
Cell Death Discov. 2025 May 21;11(1):247. doi: 10.1038/s41420-025-02535-4.
3
SDH defective cancers: molecular mechanisms and treatment strategies.琥珀酸脱氢酶缺陷型癌症：分子机制与治疗策略

本文引用的文献

1
Pathological Role of HDAC8: Cancer and Beyond.HDAC8 的病理作用：癌症及其他。
Cells. 2022 Oct 9;11(19):3161. doi: 10.3390/cells11193161.
2
Class I histone deacetylases (HDAC1-3) are histone lysine delactylases.I类组蛋白去乙酰化酶（HDAC1 - 3）是组蛋白赖氨酸去乙酰基酶。
Sci Adv. 2022 Jan 21;8(3):eabi6696. doi: 10.1126/sciadv.abi6696. Epub 2022 Jan 19.
3
Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation.定量亚细胞酰基辅酶 A 分析揭示了独特的核代谢和依赖异亮氨酸的组蛋白丙酰化。
Cell Biol Toxicol. 2025 Apr 26;41(1):74. doi: 10.1007/s10565-025-10022-w.
4
Post-translational acylation of proteins in cardiac hypertrophy.心脏肥大中蛋白质的翻译后酰化作用。
Nat Rev Cardiol. 2025 Apr 14. doi: 10.1038/s41569-025-01150-1.
5
GCLC desuccinylation regulated by oxidative stress protects human cancer cells from ferroptosis.由氧化应激调节的GCLC去琥珀酰化作用可保护人类癌细胞免受铁死亡。
Cell Death Differ. 2025 Apr 5. doi: 10.1038/s41418-025-01505-8.
6
KLF6-mediated recruitment of the p300 complex enhances H3K23su and cooperatively upregulates SEMA3C with FOSL2 to drive 5-FU resistance in colon cancer cells.KLF6介导的p300复合物募集增强H3K23su，并与FOSL2协同上调SEMA3C，以驱动结肠癌细胞中的5-氟尿嘧啶耐药。
Exp Mol Med. 2025 Mar;57(3):667-685. doi: 10.1038/s12276-025-01424-1. Epub 2025 Mar 13.
7
SENP1-SIRT3 axis mediates glycolytic reprogramming to suppress inflammation during infection.SENP1-SIRT3轴介导糖酵解重编程以在感染期间抑制炎症。
mBio. 2025 Apr 9;16(4):e0252424. doi: 10.1128/mbio.02524-24. Epub 2025 Mar 12.
8
Alterations in PD-L1 succinylation shape anti-tumor immune responses in melanoma.PD-L1琥珀酰化修饰的改变影响黑色素瘤的抗肿瘤免疫反应。
Nat Genet. 2025 Mar;57(3):680-693. doi: 10.1038/s41588-025-02077-6. Epub 2025 Mar 11.
9
Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.线粒体去乙酰化酶SIRT5在琥珀酰化修饰和癌症发展中的新作用。
Front Immunol. 2025 Jan 29;16:1531246. doi: 10.3389/fimmu.2025.1531246. eCollection 2025.
10
Unlocking the Hidden Potential of Cancer Therapy Targeting Lysine Succinylation.挖掘靶向赖氨酸琥珀酰化的癌症治疗的隐藏潜力。
J Cancer. 2025 Jan 1;16(3):821-834. doi: 10.7150/jca.105849. eCollection 2025.
Mol Cell. 2022 Jan 20;82(2):447-462.e6. doi: 10.1016/j.molcel.2021.11.006. Epub 2021 Dec 1.
4
HBO1 is a versatile histone acyltransferase critical for promoter histone acylations.HBO1 是一种多功能的组蛋白酰基转移酶，对于启动子组蛋白酰化至关重要。
Nucleic Acids Res. 2021 Aug 20;49(14):8037-8059. doi: 10.1093/nar/gkab607.
5
Histone acylations and chromatin dynamics: concepts, challenges, and links to metabolism.组蛋白酰化和染色质动力学：概念、挑战以及与代谢的联系。
EMBO Rep. 2021 Jul 5;22(7):e52774. doi: 10.15252/embr.202152774. Epub 2021 Jun 23.
6
Understanding the Function of Mammalian Sirtuins and Protein Lysine Acylation.理解哺乳动物 Sirtuins 与蛋白赖氨酸酰化作用的功能。
Annu Rev Biochem. 2021 Jun 20;90:245-285. doi: 10.1146/annurev-biochem-082520-125411. Epub 2021 Apr 13.
7
The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway.赖氨酸β-羟基丁酰化途径的调节酶和蛋白质底物。
Sci Adv. 2021 Feb 24;7(9). doi: 10.1126/sciadv.abe2771. Print 2021 Feb.
8
Twelve years of SAMtools and BCFtools.SAMtools 和 BCFtools 十二年。
Gigascience. 2021 Feb 16;10(2). doi: 10.1093/gigascience/giab008.
9
Succinylation of H3K122 destabilizes nucleosomes and enhances transcription.琥珀酰化 H3K122 会破坏核小体并增强转录。
EMBO Rep. 2021 Mar 3;22(3):e51009. doi: 10.15252/embr.202051009. Epub 2021 Jan 29.
10
Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis.组蛋白乙酰转移酶 1 是组蛋白和非组蛋白的琥珀酰转移酶，促进肿瘤发生。
EMBO Rep. 2021 Feb 3;22(2):e50967. doi: 10.15252/embr.202050967. Epub 2020 Dec 29.