造血和白血病发病机制中的 CHAF1B 依赖性分子开关
A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.
机构信息
Division of Hematology/Oncology, Northwestern University, 303 East Superior Street, 5-123, Chicago, IL 60611, USA.
Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA.
出版信息
Cancer Cell. 2018 Nov 12;34(5):707-723.e7. doi: 10.1016/j.ccell.2018.10.004.
Abstract
CHAF1B is the p60 subunit of the chromatin assembly factor (CAF1) complex, which is responsible for assembly of histones H3.1/H4 heterodimers at the replication fork during S phase. Here we report that CHAF1B is required for normal hematopoiesis while its overexpression promotes leukemia. CHAF1B has a pro-leukemia effect by binding chromatin at discrete sites and interfering with occupancy of transcription factors that promote myeloid differentiation, such as CEBPA. Reducing Chaf1b activity by either heterozygous deletion or overexpression of a CAF1 dominant negative allele is sufficient to suppress leukemogenesis in vivo without impairing normal hematopoiesis.
摘要
CHAF1B 是染色质组装因子（CAF1）复合物的 p60 亚基，它负责在 S 期的复制叉处组装组蛋白 H3.1/H4 异二聚体。在这里，我们报告 CHAF1B 是正常造血所必需的，而过表达则会促进白血病。CHAF1B 通过在离散位点结合染色质并干扰促进髓样分化的转录因子（如 CEBPA）的占据，从而发挥促白血病作用。通过杂合缺失或 CAF1 显性负等位基因的过表达降低 Chaf1b 的活性足以抑制体内白血病的发生，而不损害正常造血。
相似文献
1
A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.造血和白血病发病机制中的 CHAF1B 依赖性分子开关
Cancer Cell. 2018 Nov 12;34(5):707-723.e7. doi: 10.1016/j.ccell.2018.10.004.
2
Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development.染色质组装因子 CHAF1B 对 TRIM13 的抑制作用对 AML 的发展至关重要。
Blood Adv. 2023 Sep 12;7(17):4822-4837. doi: 10.1182/bloodadvances.2022009438.
3
CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos.CHAF1b，染色质组装因子 1 亚基 b，对小鼠植入前胚胎是必需的。
Int J Biol Macromol. 2022 Jan 15;195:547-557. doi: 10.1016/j.ijbiomac.2021.11.181. Epub 2021 Dec 11.
4
CHAF1B Overexpression: A Brake for the Differentiation of Leukemia Cells.CHAF1B 过表达：白血病细胞分化的刹车。
Cancer Cell. 2018 Nov 12;34(5):693-694. doi: 10.1016/j.ccell.2018.10.011.
5
CHAF1B promotes proliferation and reduces apoptosis in 95‑D lung cancer cells and predicts a poor prognosis in non‑small cell lung cancer.CHAF1B 促进 95-D 肺癌细胞的增殖，减少细胞凋亡，并预测非小细胞肺癌的预后不良。
Oncol Rep. 2019 Apr;41(4):2518-2528. doi: 10.3892/or.2019.6994. Epub 2019 Feb 1.
6
The role of the chromatin assembly complex (CAF-1) and its p60 subunit (CHAF1b) in homeostasis and disease.染色质组装复合物（CAF-1）及其p60亚基（CHAF1b）在体内稳态和疾病中的作用。
Biochim Biophys Acta. 2015 Aug;1849(8):979-86. doi: 10.1016/j.bbagrm.2015.05.009. Epub 2015 Jun 9.
7
Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia.解旋酶样转录因子是RUNX1的一个靶点，其下调会促进基因组不稳定，并与急性髓系白血病复杂的细胞遗传学特征相关。
Haematologica. 2016 Apr;101(4):448-57. doi: 10.3324/haematol.2015.137125. Epub 2016 Jan 22.
8
The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1.Cac2 亚基对于 CAF-1 中具有生物活性的组蛋白结合和核小体组装是必需的。
Sci Rep. 2017 Apr 18;7:46274. doi: 10.1038/srep46274.
9
CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice.CCAAT/增强子结合蛋白α（CEBPA）基因单倍体不足不会改变Lck-CALM/AF10转基因小鼠的造血功能或诱发白血病。
Braz J Med Biol Res. 2019;52(6):e8424. doi: 10.1590/1414-431X20198424. Epub 2019 May 27.
10
Dissection of the Major Hematopoietic Quantitative Trait Locus in Chromosome 6q23.3 Identifies miR-3662 as a Player in Hematopoiesis and Acute Myeloid Leukemia.对6号染色体6q23.3上主要造血数量性状位点的剖析确定miR-3662在造血和急性髓系白血病中发挥作用。
Cancer Discov. 2016 Sep;6(9):1036-51. doi: 10.1158/2159-8290.CD-16-0023. Epub 2016 Jun 27.
引用本文的文献
1
KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML.KAT6A嵌合体与NURF和MLL/COMPASS形成一个自我强化的表观遗传模块，以维持急性髓系白血病。
Genome Biol. 2025 Aug 19;26(1):253. doi: 10.1186/s13059-025-03743-y.
2
Specificity protein 1 initiates epithelial-mesenchymal transition of circulating tumor cells to inhibit metastasis in prostate cancer.特异性蛋白1启动循环肿瘤细胞的上皮-间质转化以抑制前列腺癌转移。
Cancer Cell Int. 2025 Jul 11;25(1):255. doi: 10.1186/s12935-025-03888-7.
3
Histone chaperones coupled to DNA replication and transcription control divergent chromatin elements to maintain cell fate.与DNA复制和转录相关联的组蛋白伴侣调控不同的染色质元件以维持细胞命运。
Genes Dev. 2025 May 2;39(9-10):652-675. doi: 10.1101/gad.352316.124.
4
Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations.远距离增强子控制的基因对调控因子扰动高度敏感。
Cell Genom. 2025 Mar 12;5(3):100778. doi: 10.1016/j.xgen.2025.100778. Epub 2025 Feb 25.
5
CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.CHAF1B通过抑制SETD7的表达促进肺鳞状细胞癌的进展。
Front Med. 2025 Apr;19(2):318-328. doi: 10.1007/s11684-024-1122-2. Epub 2025 Jan 25.
6
Integrated bioinformatics and experimental analysis of CHAF1B as a novel biomarker and immunotherapy target in LUAD.CHAF1B作为肺腺癌新生物标志物和免疫治疗靶点的综合生物信息学与实验分析
Discov Oncol. 2025 Jan 14;16(1):43. doi: 10.1007/s12672-025-01767-1.
7
Chromatin assembly factor 1 suppresses epigenetic reprogramming toward adaptive drug resistance.染色质组装因子1抑制向适应性耐药的表观遗传重编程。
J Natl Cancer Cent. 2021 Jan 16;1(1):15-22. doi: 10.1016/j.jncc.2020.12.003. eCollection 2021 Mar.
8
Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.癌症中拷贝数改变的临床、生物学和治疗影响的见解。
Int J Mol Sci. 2024 Jun 21;25(13):6815. doi: 10.3390/ijms25136815.
9
The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.TLK-ASF1 组蛋白伴侣途径在 IL-1β 介导的 AML 进展中发挥关键作用。
Blood. 2024 Jun 27;143(26):2749-2762. doi: 10.1182/blood.2023022079.
10
miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.微小RNA作为小儿急性淋巴细胞白血病治疗反应的预测生物标志物
Oncol Lett. 2023 Dec 21;27(2):71. doi: 10.3892/ol.2023.14204. eCollection 2024 Feb.
本文引用的文献
1
Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation.Asf1a 解析二价染色质结构域，以促进小鼠胚胎干细胞分化过程中谱系特异性基因的表达。
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6162-E6171. doi: 10.1073/pnas.1801909115. Epub 2018 Jun 18.
2
The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1.Cac2 亚基对于 CAF-1 中具有生物活性的组蛋白结合和核小体组装是必需的。
Sci Rep. 2017 Apr 18;7:46274. doi: 10.1038/srep46274.
3
DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication.DNA介导的酵母染色质组装因子1（CAF-1）的两个组蛋白结合复合物的缔合在DNA复制后驱动四体组装。
Elife. 2017 Mar 18;6:e22799. doi: 10.7554/eLife.22799.
4
Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution.谱系特异性和单细胞染色质可及性图谱描绘了人类造血作用和白血病的演变。
Nat Genet. 2016 Oct;48(10):1193-203. doi: 10.1038/ng.3646. Epub 2016 Aug 15.
5
Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers.ORC结合位点的选择性及其与复制时间、脆性位点和癌症中缺失的关系。
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4810-9. doi: 10.1073/pnas.1609060113. Epub 2016 Jul 19.
6
Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells.释放的Bim与Mcl-1的结合是AML细胞对ABT-199产生内在抗性的一种机制，而在AML细胞中与柔红霉素或阿糖胞苷联合使用可克服这种抗性。
Clin Cancer Res. 2016 Sep 1;22(17):4440-51. doi: 10.1158/1078-0432.CCR-15-3057. Epub 2016 Apr 21.
7
The histone chaperone CAF-1 safeguards somatic cell identity.组蛋白伴侣CAF-1维护体细胞身份。
Nature. 2015 Dec 10;528(7581):218-24. doi: 10.1038/nature15749.
8
Meta- and Orthogonal Integration of Influenza "OMICs" Data Defines a Role for UBR4 in Virus Budding.流感“组学”数据的元整合与正交整合确定了UBR4在病毒出芽中的作用。
Cell Host Microbe. 2015 Dec 9;18(6):723-35. doi: 10.1016/j.chom.2015.11.002.
9
Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.有丝分裂转录激活：通过有丝分裂中的转录延伸控制清除活跃结合的RNA聚合酶II
Mol Cell. 2015 Nov 5;60(3):435-45. doi: 10.1016/j.molcel.2015.09.021.
10
Systematic identification of factors for provirus silencing in embryonic stem cells.胚胎干细胞中前病毒沉默因子的系统鉴定
Cell. 2015 Sep 24;163(1):230-45. doi: 10.1016/j.cell.2015.08.037. Epub 2015 Sep 10.
Zotero 插件