The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability

Huang Yun; Mouttet Brice; Warnatz Hans-Joerg; Risch Thomas; Rietmann Fabian; Frommelt Fabian; Ngo Quy A.; Dobay Maria Pamela; Marovca Blerim; Jenni Silvia; Tsai Yi-Chien; Matzk Soeren; Amstislavskiy Vyacheslav; Schrappe Martin; Stanulla Martin; Gstaiger Matthias; Bornhauser Beat; Yaspo Marie-Laure; Bourquin Jean-Pierre

首页> 外文期刊>Cancer Cell >The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability

【24h】

The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability

机译：白血动性TCF3-HLF复合重丝旋转增强剂驾驶蜂窝身份和自我更新赋予EP300脆弱性

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

The chimeric transcription factor TCF3-HLF defines an incurable acute lymphoblastic leukemia subtype. Here we decipher the regulome of endogenous TCF3-HLF and dissect its essential transcriptional components and targets by functional genomics. We demonstrate that TCF3-HLF recruits HLF binding sites at hematopoietic stem cell/myeloid lineage associated (super-) enhancers to drive lineage identity and self-renewal. Among direct targets, hijacking an HLF binding site in a MYC enhancer cluster by TCF3-HLF activates a conserved MYC-driven transformation program crucial for leukemia propagation in vivo. TCF3-HLF pioneers the cooperation with ERG and recruits histone acetyltransferase p300 (EP300), conferring susceptibility to EP300 inhibition. Our study provides a framework for targeting driving transcriptional dependencies in this fatal leukemia.

机译：嵌合转录因子TCF3-HLF定义了一种不可治愈的急性淋巴细胞白血病亚型。在这里，我们破译内源性TCF3-HLF的调控，并通过功能基因组学分析其关键转录成分和靶点。我们证明TCF3-HLF在造血干细胞/髓系相关（超级）增强子处招募HLF结合位点，以驱动谱系认同和自我更新。在直接靶点中，TCF3-HLF劫持MYC增强子簇中的HLF结合位点激活了一个保守的MYC驱动的转化程序，该程序对白血病在体内的传播至关重要。TCF3-HLF开创了与ERG的合作，并招募了组蛋白乙酰转移酶p300（EP300），赋予其对EP300抑制的敏感性。我们的研究为在这种致命的白血病中定位驱动转录依赖性提供了一个框架。

著录项

来源
《Cancer Cell》 |2019年第6期|共24页
作者
Huang Yun; Mouttet Brice; Warnatz Hans-Joerg; Risch Thomas; Rietmann Fabian; Frommelt Fabian; Ngo Quy A.; Dobay Maria Pamela; Marovca Blerim; Jenni Silvia; Tsai Yi-Chien; Matzk Soeren; Amstislavskiy Vyacheslav; Schrappe Martin; Stanulla Martin; Gstaiger Matthias; Bornhauser Beat; Yaspo Marie-Laure; Bourquin Jean-Pierre;
展开▼
作者单位

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Childrens Res Ctr CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Childrens Res Ctr CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Swiss Fed Inst Technol Dept Biol Inst Mol Syst Biol CH-8093 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Childrens Res Ctr CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Childrens Res Ctr CH-8032 Zurich Switzerland;

Christian Albrecht Univ Kiel Dept Pediat D-24105 Kiel Germany;

Hannover Med Sch Pediat Hematol &

Oncol D-30625 Hannover Germany;

Swiss Fed Inst Technol Dept Biol Inst Mol Syst Biol CH-8093 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Childrens Res Ctr CH-8032 Zurich Switzerland;

Univ Childrens Hosp Zurich Div Oncol CH-8032 Zurich Switzerland;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类肿瘤学;
关键词

相似文献

外文文献
专利

1. ENHANCED EXPRESSION OF hALP GENE CONFERS CELLULAR RESISTANCE TO H2O2 INDUCED SENESCENCE [J] . Yun, Ling, Hai-jing, 中国医学科学杂志：英文版 . 2006,第001期
2. ENHANCED EXPRESSION OF hALP GENE CONFERS CELLULAR RESISTANCE TO H2O2 INDUCED SENESCENCE [J] . 中国医学科学杂志（英文版） . 2006,第001期
3. NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly [J] . Tingting Hou, Xianhua Wang, Rufeng Zhang, 细胞研究（英文版） . 2019,第009期
4. THE LEUKEMIA-DRIVING FUSION PROTEIN TCF3-HLF IS REGULATED BY EP300 [J] . Cancer discovery. . 2020,第1期

机译：白血病驱动融合蛋白TCF3-HLF由EP300调节
5. ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia [J] . Thirant Cecile, Ignacimouttou Cathy, Lopez Cecile K., Cancer Cell . 2017,第3期

机译：Eto2-Glis2劫持转录复合物，以驱动细胞身份和小儿急性巨大巨大白血病的自我更新
6. ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia [J] . Thirant Cecile, Ignacimouttou Cathy, Lopez Cecile K., Cancer Cell . 2017,第3期

机译：Eto2-Glis2劫持转录复合物，以驱动细胞身份和小儿急性巨大巨大白血病的自我更新
7. Enhancing Complex Network Controllability by Rewiring Links [C] . Lvlin Hou, Songyang Lao, Jiang Bu, 2013 Third International Conference on Intelligent System Design and Engineering Applications. . 2013

机译：通过重新链接来增强复杂的网络可控性
8. Complex, tissue-specific gene regulation conferred by the androgen-dependent enhancer of the mouse sex-limited protein (Slp) gene [D] . Nelson, Stefanie Ann 1996

机译：小鼠性别限制蛋白（Slp）基因的雄激素依赖性增强子赋予复杂的组织特异性基因调控
9. Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development [O] . Neil A. Barrett, Camille Malouf, Chrysa Kapeni, -1

机译：Mll-AF4在受限的开发窗口中赋予增强的自我更新和淋巴潜能
10. Mll-AF4 confers enhanced self-renewal and lymphoid potential during a restricted window in development [O] . Barrett Neil A, Malouf Camille, Kapeni Chrysoula, 2016

机译：Mll-AF4在受限的发育期中赋予增强的自我更新和淋巴样潜能

The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability

摘要

著录项

相似文献

相关主题

期刊订阅