• 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

在造血前体细胞中失去 H3.3 伴侣蛋白 Daxx 后，染色质景观发生异常，导致 Pu.1 介导的中性粒细胞增多和炎症。

Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation.

机构信息

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Department of Cancer Biology, UCL Cancer Institute, London, UK.

出版信息

Nat Cell Biol. 2021 Dec;23(12):1224-1239. doi: 10.1038/s41556-021-00774-y. Epub 2021 Dec 7.

DOI:10.1038/s41556-021-00774-y
PMID:34876685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8683376/
Abstract

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.

摘要

逆转录转座子的沉默缺陷与炎症、癌症和自身免疫性疾病有关。然而，其潜在机制尚不完全清楚。在这里，我们将组蛋白 H3.3 伴侣 Daxx 牵连进来，Daxx 是一种在髓性白血病和其他肿瘤中失活的逆转录转座子抑制剂，它可以保护免受炎症性疾病的侵害。Daxx 的缺失会改变造血祖细胞的染色质景观、H3.3 分布和组蛋白标记，导致 Pu.1 依赖性的髓系细胞生成转录程序的激活，而牺牲了 B 细胞分化。这会导致嗜中性粒细胞增多和炎症，使小鼠易患自身炎症性皮肤病。虽然在同时缺乏 Pu.1 和 Daxx 的动物中，这些分子和表型的改变在一定程度上得到了逆转，但这些小鼠的造血祖细胞表现出独特的染色质和转录组改变，这表明这两种途径之间存在相互作用。总的来说，我们的研究结果表明逆转录转座子沉默在造血中起作用，并提示 H3.3 加载机制与先驱转录因子 Pu.1 之间存在相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/f4318c3477f4/41556_2021_774_Fig18_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/7ac527d41f16/41556_2021_774_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/915136962795/41556_2021_774_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/dae38dbf43bc/41556_2021_774_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/5c14d0c9f8c9/41556_2021_774_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/70af7816f72b/41556_2021_774_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/688d36b4b25f/41556_2021_774_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/0aa4eee3289f/41556_2021_774_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/4af276e66118/41556_2021_774_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/8197e97ec9fe/41556_2021_774_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/223f775a2636/41556_2021_774_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/f7850155a830/41556_2021_774_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/d24257eca378/41556_2021_774_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/67e7e50d8e6d/41556_2021_774_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/2b5200c5f2f3/41556_2021_774_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/cd060ae7daef/41556_2021_774_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/46adc6c71b95/41556_2021_774_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/d7f53e563ec1/41556_2021_774_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/f4318c3477f4/41556_2021_774_Fig18_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/7ac527d41f16/41556_2021_774_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/915136962795/41556_2021_774_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/dae38dbf43bc/41556_2021_774_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/5c14d0c9f8c9/41556_2021_774_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/70af7816f72b/41556_2021_774_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/688d36b4b25f/41556_2021_774_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/0aa4eee3289f/41556_2021_774_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/4af276e66118/41556_2021_774_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/8197e97ec9fe/41556_2021_774_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/223f775a2636/41556_2021_774_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/f7850155a830/41556_2021_774_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/d24257eca378/41556_2021_774_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/67e7e50d8e6d/41556_2021_774_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/2b5200c5f2f3/41556_2021_774_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/cd060ae7daef/41556_2021_774_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/46adc6c71b95/41556_2021_774_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/d7f53e563ec1/41556_2021_774_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9259/8683376/f4318c3477f4/41556_2021_774_Fig18_ESM.jpg

相似文献

1
Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation.在造血前体细胞中失去 H3.3 伴侣蛋白 Daxx 后，染色质景观发生异常，导致 Pu.1 介导的中性粒细胞增多和炎症。
Nat Cell Biol. 2021 Dec;23(12):1224-1239. doi: 10.1038/s41556-021-00774-y. Epub 2021 Dec 7.
2
Histone variant H3.3 maintains adult haematopoietic stem cell homeostasis by enforcing chromatin adaptability.组蛋白变体 H3.3 通过加强染色质的适应性来维持成体造血干细胞的内稳态。
Nat Cell Biol. 2022 Jan;24(1):99-111. doi: 10.1038/s41556-021-00795-7. Epub 2021 Dec 27.
3
PML is recruited to heterochromatin during S phase and represses DAXX-mediated histone H3.3 chromatin assembly.PML 在 S 期被招募到异染色质中，并抑制 DAXX 介导的组蛋白 H3.3 染色质组装。
J Cell Sci. 2019 Mar 26;132(6):jcs220970. doi: 10.1242/jcs.220970.
4
The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3.死亡相关蛋白 DAXX 是一种新型组蛋白伴侣，参与复制独立的 H3.3 沉积。
Genes Dev. 2010 Jun 15;24(12):1253-65. doi: 10.1101/gad.566910. Epub 2010 May 26.
5
Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation.钙依赖性去磷酸化组蛋白伴侣 DAXX 调节神经元激活时 H3.3 的加载和转录。
Neuron. 2012 Apr 12;74(1):122-35. doi: 10.1016/j.neuron.2012.02.021.
6
Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage.由胚胎干细胞阶段的表观遗传标记引发的活性组织特异性染色质结构域的形成。
Mol Cell Biol. 2005 Mar;25(5):1804-20. doi: 10.1128/MCB.25.5.1804-1820.2005.
7
HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.HIRA 与 DAXX：塑造组蛋白 H3.3 景观的两个轴。
Exp Mol Med. 2024 Feb;56(2):251-263. doi: 10.1038/s12276-023-01145-3. Epub 2024 Feb 1.
8
Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation.Morc3 通过促进 Daxx 介导的组蛋白 H3.3 掺入来沉默内源性逆转录病毒。
Nat Commun. 2021 Oct 14;12(1):5996. doi: 10.1038/s41467-021-26288-7.
9
Author Correction: Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation.作者更正：造血前体细胞中H3.3伴侣蛋白Daxx缺失后异常的染色质景观导致Pu.1介导的中性粒细胞增多和炎症。
Nat Cell Biol. 2022 Jan;24(1):123. doi: 10.1038/s41556-021-00833-4.
10
DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network.DAXX 添加了一个从头开始的 H3.3K9me3 沉积途径到组蛋白伴侣网络。
Mol Cell. 2023 Apr 6;83(7):1075-1092.e9. doi: 10.1016/j.molcel.2023.02.009. Epub 2023 Mar 2.

引用本文的文献

1
SUMO operates from a unique long tandem repeat to keep innate immunity in check.小泛素样修饰蛋白（SUMO）通过一个独特的长串联重复序列发挥作用，以控制先天免疫。
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf750.
2
Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation.组蛋白变体：细胞去分化和转分化过程中炎症的关键调节因子。
Front Immunol. 2025 Jun 27;16:1619100. doi: 10.3389/fimmu.2025.1619100. eCollection 2025.
3
Age and Sex Effects on Blood Retrotransposable Element Expression Levels: Findings From the Population-Based Rhineland Study.

本文引用的文献

1
Repetitive Elements Trigger RIG-I-like Receptor Signaling that Regulates the Emergence of Hematopoietic Stem and Progenitor Cells.重复元件触发 RIG-I 样受体信号通路，调节造血干/祖细胞的出现。
Immunity. 2020 Nov 17;53(5):934-951.e9. doi: 10.1016/j.immuni.2020.10.007. Epub 2020 Nov 6.
2
HIRA, a DiGeorge Syndrome Candidate Gene, Confers Proper Chromatin Accessibility on HSCs and Supports All Stages of Hematopoiesis.HIRA，一个 DiGeorge 综合征候选基因，赋予 HSCs 适当的染色质可及性，并支持造血的所有阶段。
Cell Rep. 2020 Feb 18;30(7):2136-2149.e4. doi: 10.1016/j.celrep.2020.01.062.
3
Interferon-Independent Innate Responses to Cytomegalovirus.
年龄和性别对血液逆转录转座元件表达水平的影响：基于人群的莱茵兰研究结果
Aging Cell. 2025 Aug;24(8):e70092. doi: 10.1111/acel.70092. Epub 2025 May 4.
4
Histone methyltransferase SETDB1 safeguards mouse fetal hematopoiesis by suppressing activation of cryptic enhancers.组蛋白甲基转移酶SETDB1通过抑制隐匿性增强子的激活来保护小鼠胎儿造血。
Proc Natl Acad Sci U S A. 2024 Dec 24;121(52):e2409656121. doi: 10.1073/pnas.2409656121. Epub 2024 Dec 17.
5
Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration.干细胞活性耦合的内源性逆转录病毒抑制调控成年组织再生。
Cell. 2024 Dec 26;187(26):7414-7432.e26. doi: 10.1016/j.cell.2024.10.007. Epub 2024 Oct 29.
6
Plasma cell differentiation is regulated by the expression of histone variant H3.3.浆细胞分化受组蛋白变体 H3.3 的表达调控。
Nat Commun. 2024 Jun 20;15(1):5004. doi: 10.1038/s41467-024-49375-x.
7
HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.HIRA 与 DAXX：塑造组蛋白 H3.3 景观的两个轴。
Exp Mol Med. 2024 Feb;56(2):251-263. doi: 10.1038/s12276-023-01145-3. Epub 2024 Feb 1.
8
(B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.（B）单共组蛋白与骨癌根源处的表观遗传改变。
Cell Death Differ. 2025 Jan;32(1):66-77. doi: 10.1038/s41418-023-01227-9. Epub 2023 Oct 12.
9
The cell-cycle choreography of H3 variants shapes the genome.H3 变体的细胞周期编排塑造了基因组。
Mol Cell. 2023 Nov 2;83(21):3773-3786. doi: 10.1016/j.molcel.2023.08.030. Epub 2023 Sep 20.
10
The histone chaperone function of Daxx is dispensable for embryonic development.Daxx 的组蛋白伴侣功能对于胚胎发育并非必需。
Cell Death Dis. 2023 Aug 26;14(8):565. doi: 10.1038/s41419-023-06089-0.
巨细胞病毒的干扰素非依赖型先天免疫反应
Front Immunol. 2019 Dec 11;10:2751. doi: 10.3389/fimmu.2019.02751. eCollection 2019.
4
GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis.GM-CSF 驱动实验性脊柱关节炎中失调的造血干细胞活性和病理性骨髓外髓系生成。
Nat Commun. 2020 Jan 9;11(1):155. doi: 10.1038/s41467-019-13853-4.
5
ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures.ATRX 框内融合神经母细胞瘤通过调节神经元基因特征对 EZH2 抑制敏感。
Cancer Cell. 2019 Nov 11;36(5):512-527.e9. doi: 10.1016/j.ccell.2019.09.002. Epub 2019 Oct 17.
6
Mechanisms of Inflammation in Neutrophil-Mediated Skin Diseases.中性粒细胞介导的皮肤疾病中的炎症机制。
Front Immunol. 2019 May 8;10:1059. doi: 10.3389/fimmu.2019.01059. eCollection 2019.
7
CUT&Tag for efficient epigenomic profiling of small samples and single cells.CUT&Tag 技术可高效地对小样本和单细胞进行表观基因组分析。
Nat Commun. 2019 Apr 29;10(1):1930. doi: 10.1038/s41467-019-09982-5.
8
Neutrophils and NETs in modulating acute and chronic inflammation.中性粒细胞和 NETs 在调节急性和慢性炎症中的作用。
Blood. 2019 May 16;133(20):2178-2185. doi: 10.1182/blood-2018-11-844530. Epub 2019 Mar 21.
9
Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.H3.3 组蛋白伴侣复合物 HIRA 的功能活性需要 HIRA 亚基的三聚化。
Nat Commun. 2018 Aug 6;9(1):3103. doi: 10.1038/s41467-018-05581-y.
10
Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors.髓系分化过程中增强子和转录因子的动态变化揭示了 Cebpa 缺失祖细胞中的早期分化阻滞。
Cell Rep. 2018 May 29;23(9):2744-2757. doi: 10.1016/j.celrep.2018.05.012.