• 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

依赖复合物的组蛋白乙酰转移酶活性 KAT8 决定了其在转录和细胞内稳态中的作用。

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis.

机构信息

Cell Biology Program and Center for Epigenetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N 2200, Denmark; The Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, Copenhagen N 2200, Denmark.

Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Odense 5230, Denmark; Microchemistry and Proteomics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

出版信息

Mol Cell. 2021 Apr 15;81(8):1749-1765.e8. doi: 10.1016/j.molcel.2021.02.012. Epub 2021 Mar 2.

DOI:10.1016/j.molcel.2021.02.012
PMID:33657400
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8056186/
Abstract

Acetylation of lysine 16 on histone H4 (H4K16ac) is catalyzed by histone acetyltransferase KAT8 and can prevent chromatin compaction in vitro. Although extensively studied in Drosophila, the functions of H4K16ac and two KAT8-containing protein complexes (NSL and MSL) are not well understood in mammals. Here, we demonstrate a surprising complex-dependent activity of KAT8: it catalyzes H4K5ac and H4K8ac as part of the NSL complex, whereas it catalyzes the bulk of H4K16ac as part of the MSL complex. Furthermore, we show that MSL complex proteins and H4K16ac are not required for cell proliferation and chromatin accessibility, whereas the NSL complex is essential for cell survival, as it stimulates transcription initiation at the promoters of housekeeping genes. In summary, we show that KAT8 switches catalytic activity and function depending on its associated proteins and that, when in the NSL complex, it catalyzes H4K5ac and H4K8ac required for the expression of essential genes.

摘要

组蛋白 H4 赖氨酸 16 的乙酰化（H4K16ac）由组蛋白乙酰转移酶 KAT8 催化，可防止体外染色质紧缩。尽管在果蝇中得到了广泛研究，但 H4K16ac 和两个包含 KAT8 的蛋白复合物（NSL 和 MSL）的功能在哺乳动物中尚未得到很好的理解。在这里，我们证明了 KAT8 令人惊讶的依赖复合物的活性：它作为 NSL 复合物的一部分催化 H4K5ac 和 H4K8ac，而作为 MSL 复合物的一部分则催化大部分 H4K16ac。此外，我们表明，MSL 复合物蛋白和 H4K16ac 不参与细胞增殖和染色质可及性，而 NSL 复合物对于细胞存活至关重要，因为它刺激了管家基因启动子处的转录起始。总之，我们表明 KAT8 根据其相关蛋白改变催化活性和功能，并且当它处于 NSL 复合物中时，它催化 H4K5ac 和 H4K8ac，这是表达必需基因所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/3a63b191abd6/nihms-1674320-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/f56daceced87/nihms-1674320-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/b3009cddc30a/nihms-1674320-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/24c8c3fb28eb/nihms-1674320-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/c36b0f21e77e/nihms-1674320-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/384cc840656f/nihms-1674320-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/5597b8a3abf4/nihms-1674320-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/3a63b191abd6/nihms-1674320-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/f56daceced87/nihms-1674320-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/b3009cddc30a/nihms-1674320-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/24c8c3fb28eb/nihms-1674320-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/c36b0f21e77e/nihms-1674320-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/384cc840656f/nihms-1674320-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/5597b8a3abf4/nihms-1674320-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c6/8056186/3a63b191abd6/nihms-1674320-f0008.jpg

相似文献

1
Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis.依赖复合物的组蛋白乙酰转移酶活性 KAT8 决定了其在转录和细胞内稳态中的作用。
Mol Cell. 2021 Apr 15;81(8):1749-1765.e8. doi: 10.1016/j.molcel.2021.02.012. Epub 2021 Mar 2.
2
Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation.与Mof相关的复合物在调节胚胎干细胞的多能性以及分化过程中具有重叠且独特的作用。
Elife. 2014 Jun 4;3:e02104. doi: 10.7554/eLife.02104.
3
Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila.果蝇中由 5' 连接的 Gal4-MOF 组蛋白乙酰转移酶融合蛋白介导的性别偏向转录增强。
BMC Mol Biol. 2010 Nov 9;11:80. doi: 10.1186/1471-2199-11-80.
4
KAT8 is upregulated and recruited to the promoter of Atg8 by FOXO to induce H4 acetylation for autophagy under 20-hydroxyecdysone regulation.KAT8 通过 FOXO 被上调并募集到 Atg8 的启动子上，以在 20-羟基蜕皮酮调节下诱导自噬的 H4 乙酰化。
J Biol Chem. 2024 Mar;300(3):105704. doi: 10.1016/j.jbc.2024.105704. Epub 2024 Feb 1.
5
Crosstalk between NSL histone acetyltransferase and MLL/SET complexes: NSL complex functions in promoting histone H3K4 di-methylation activity by MLL/SET complexes.NSL 组蛋白乙酰转移酶与 MLL/SET 复合物之间的串扰：NSL 复合物通过 MLL/SET 复合物促进组蛋白 H3K4 二甲基化活性。
PLoS Genet. 2013 Nov;9(11):e1003940. doi: 10.1371/journal.pgen.1003940. Epub 2013 Nov 14.
6
Hotspot Cancer Mutation Impairs KAT8-mediated Nucleosomal Histone Acetylation.热点癌症突变削弱 KAT8 介导的核小体组蛋白乙酰化。
J Mol Biol. 2024 Apr 1;436(7):168413. doi: 10.1016/j.jmb.2023.168413. Epub 2023 Dec 20.
7
KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health.KAT8 超越乙酰化：对其表观遗传调控、遗传变异性及其对人类健康影响的综述。
Genes (Basel). 2024 May 17;15(5):639. doi: 10.3390/genes15050639.
8
Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development.组蛋白乙酰转移酶 MOF 协调致癌作用、DNA 损伤反应、增殖和干细胞发育交汇点的结果。
Mol Cell Biol. 2020 Aug 28;40(18). doi: 10.1128/MCB.00232-20.
9
The non-specific lethal (NSL) complex at the crossroads of transcriptional control and cellular homeostasis.非特异性致死 (NSL) 复合物处于转录控制和细胞内稳态的交汇点。
EMBO Rep. 2019 Jul;20(7):e47630. doi: 10.15252/embr.201847630. Epub 2019 Jun 3.
10
The NSL complex regulates housekeeping genes in Drosophila.NSL 复合物在果蝇中调节管家基因。
PLoS Genet. 2012;8(6):e1002736. doi: 10.1371/journal.pgen.1002736. Epub 2012 Jun 14.

引用本文的文献

1
Histone H3K27 acetylation mediated by KAT8 maintains antiviral trained immunity in shrimp induced by inactivated white spot syndrome virus.由KAT8介导的组蛋白H3K27乙酰化维持对虾中由灭活的白斑综合征病毒诱导的抗病毒训练免疫。
Commun Biol. 2025 Aug 30;8(1):1314. doi: 10.1038/s42003-025-08767-5.
2
Fto-mediated mA modification is essential for cerebellar development through regulating epigenetic reprogramming.Fto介导的mA修饰通过调节表观遗传重编程对小脑发育至关重要。
J Biomed Sci. 2025 Aug 29;32(1):81. doi: 10.1186/s12929-025-01176-0.
3
From Lineage to Longevity: A Field Guide to the Key Players in Epigenetic Contribution to Offspring Health.

本文引用的文献

1
An integrative ENCODE resource for cancer genomics.癌症基因组学的综合 ENCODE 资源。
Nat Commun. 2020 Jul 29;11(1):3696. doi: 10.1038/s41467-020-14743-w.
2
Histone Acetyltransferase MOF Blocks Acquisition of Quiescence in Ground-State ESCs through Activating Fatty Acid Oxidation.组蛋白乙酰转移酶 MOF 通过激活脂肪酸氧化阻止静息态胚胎干细胞进入静息状态。
Cell Stem Cell. 2020 Sep 3;27(3):441-458.e10. doi: 10.1016/j.stem.2020.06.005. Epub 2020 Jun 30.
3
Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation.
从谱系到长寿：表观遗传学对后代健康影响的关键因素实用指南
Curr Issues Mol Biol. 2025 Apr 30;47(5):323. doi: 10.3390/cimb47050323.
4
Mutant EZH2 alters the epigenetic network and increases epigenetic heterogeneity in B cell lymphoma.突变型EZH2改变表观遗传网络并增加B细胞淋巴瘤中的表观遗传异质性。
PLoS Biol. 2025 Jun 12;23(6):e3003191. doi: 10.1371/journal.pbio.3003191. eCollection 2025 Jun.
5
Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9.天麻素通过靶向KAT8抑制H3K9乳酸化来减轻类风湿性关节炎。
Front Pharmacol. 2025 Mar 27;16:1559744. doi: 10.3389/fphar.2025.1559744. eCollection 2025.
6
Deep learning prioritizes cancer mutations that alter protein nucleocytoplasmic shuttling to drive tumorigenesis.深度学习对改变蛋白质核质穿梭以驱动肿瘤发生的癌症突变进行优先排序。
Nat Commun. 2025 Mar 14;16(1):2511. doi: 10.1038/s41467-025-57858-8.
7
KAT8 catalyzes the acetylation of SEPP1 at lysine 247/249 and modulates the activity of CD8 T cells via LRP8 to promote anti-tumor immunity in pancreatic cancer.KAT8催化SEPP1赖氨酸247/249位点的乙酰化，并通过LRP8调节CD8 T细胞的活性，以促进胰腺癌的抗肿瘤免疫。
Cell Biosci. 2025 Feb 19;15(1):24. doi: 10.1186/s13578-025-01356-3.
8
Modulation of the substrate preference of a MYST acetyltransferase by a scaffold protein.支架蛋白对MYST乙酰转移酶底物偏好性的调控
J Biol Chem. 2025 Mar;301(3):108262. doi: 10.1016/j.jbc.2025.108262. Epub 2025 Feb 3.
9
Basic Epigenetic Mechanisms.基本表观遗传机制
Subcell Biochem. 2025;108:1-49. doi: 10.1007/978-3-031-75980-2_1.
10
Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.致癌性异柠檬酸脱氢酶1（IDH1）导致组蛋白乙酰化显著丧失，并增加染色质异质性。
Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2403862122. doi: 10.1073/pnas.2403862122. Epub 2024 Dec 30.
进化保守的 NSL 复合物/BRD4 轴通过组蛋白乙酰化控制转录激活。
Nat Commun. 2020 May 7;11(1):2243. doi: 10.1038/s41467-020-16103-0.
4
PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia.PRMT5 甲基化组谱分析揭示了急性髓系白血病中剪接调控的直接联系。
Nat Struct Mol Biol. 2019 Nov;26(11):999-1012. doi: 10.1038/s41594-019-0313-z. Epub 2019 Oct 14.
5
Bromodomain biology and drug discovery.溴结构域生物学与药物发现。
Nat Struct Mol Biol. 2019 Oct;26(10):870-879. doi: 10.1038/s41594-019-0309-8. Epub 2019 Oct 3.
6
The NSL complex maintains nuclear architecture stability via lamin A/C acetylation.核小体稳定复合物通过核纤层蛋白 A/C 的乙酰化作用维持核架构稳定性。
Nat Cell Biol. 2019 Oct;21(10):1248-1260. doi: 10.1038/s41556-019-0397-z. Epub 2019 Oct 1.
7
Organization of Chromatin by Intrinsic and Regulated Phase Separation.染色质的固有和调控相分离组织。
Cell. 2019 Oct 3;179(2):470-484.e21. doi: 10.1016/j.cell.2019.08.037. Epub 2019 Sep 19.
8
The non-specific lethal (NSL) complex at the crossroads of transcriptional control and cellular homeostasis.非特异性致死 (NSL) 复合物处于转录控制和细胞内稳态的交汇点。
EMBO Rep. 2019 Jul;20(7):e47630. doi: 10.15252/embr.201847630. Epub 2019 Jun 3.
9
The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise.NSL 复合物介导的核小体景观对于维持转录保真度和抑制转录噪声是必需的。
Genes Dev. 2019 Apr 1;33(7-8):452-465. doi: 10.1101/gad.321489.118. Epub 2019 Feb 28.
10
The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads.Rsubread 软件包在 RNA 测序reads 的比对和定量方面，具有更简单、更快、更便宜和更好的优势。
Nucleic Acids Res. 2019 May 7;47(8):e47. doi: 10.1093/nar/gkz114.