CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia

Author:

Luo Huacheng1,Wang Fei12,Zha Jie13,Li Haoli14,Yan Bowen5,Du Qinghua6,Yang Fengchun6,Sobh Amin7,Vulpe Christopher7,Drusbosky Leylah8,Cogle Christopher8,Chepelev Iouri9,Xu Bing3,Nimer Stephen D.6,Licht Jonathan810,Qiu Yi510,Chen Baoan2,Xu Mingjiang6,Huang Suming11011ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL;

2. Department of Hematology and Oncology, The Affiliated Zhongda Hospital, Southeast University Medical School, Nanjing, China;

3. Department of Hematology, The First Affiliate Hospital of Xiamen University, Xiamen, China;

4. Department of Genetics, Southern Medical University, Guangzhou, China;

5. Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL;

6. Department of Biochemistry and Molecular Biology, University of Miami Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL;

7. Department of Physiological Sciences, University of Florida, Gainesville, FL;

8. Division of Hematology/Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL;

9. Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

10. University of Florida Health Cancer Center, University of Florida College of Medicine, Gainesville, FL; and

11. Macau Institute for Applied Research in Medicine and Health, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau

Abstract

Key Points CRISPR-Cas9 library screening identifies CBS7/9 boundary that defines an aberrant HOXA chromatin domain and HOX gene transcription in AML. Attenuation of CBS7/9 boundary impairs the leukemic transcription program and attenuates leukemic progressions in AML mouse models.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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