基因组H3.3K36M突变重新编程了冠状细胞瘤的表观基因组

Dong Fang ¹, Haiyun Gan ¹, Jeong-Heon Lee ²

¹Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
²Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Epigenomics Program, Center of Individualized Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
³Department of Orthopedic Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
⁴Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota at Twin Cities, Minneapolis, MN 55455, USA.
⁵National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China. University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.
⁶National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China.
⁷Division of Hematology/Oncology, Mayo Clinic Arizona, 13400 East Shea B., Scottsdale, AZ 85259, USA.
⁸Robert J. Tomsich Pathology and Laboratory Medicine Institute and Department of Cancer Biology, Cleveland Clinic and Lerner Research Institute, L2 9500 Euclid Avenue, Cleveland, OH 44195, USA.
⁹Departments of Pathology and Microbiology, Pediatrics, and Orthopaedic Surgery and Rehabilitation.
¹⁰Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
¹¹Epigenomics Program, Center of Individualized Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Department of Physiology and Biomedical Engineering, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Interdisciplinary Health Science Initiative, 1110 Micro and Nanotechnology Laboratory, M/C 249, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
¹²Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Department of Orthopedic Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
¹³Department of Orthopedic Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
¹⁴Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Epigenomics Program, Center of Individualized Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. zhang.zhiguo@mayo.edu.

⁰Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.

冠状细胞瘤中的H3. 3K36M突变破坏了基因组甲基化,导致基因表达变化和癌症特征. 这种表观遗传重编程有助于瘤的发展.

科学领域

癌症学
表观遗传学
分子生物学

背景情况

冠状母细胞瘤经常存在H3.3基因组变异的特定突变 (H3.3K36M).
在基因调节和瘤抑制中发挥关键作用.

研究的目的

调查H3.3K36M突变如何影响H3K36甲基化模式.
阐明改变H3K36甲基化的功能后果.

主要方法

在人类冠状细胞瘤和突变冠状细胞中分析H3K36甲基化水平.
评估H3.3K36M蛋白对H3K36甲基转移酶 (MMSET和SETD2) 的影响.
评估H3.3K36M冠状细胞中的基因表达变化和癌症相关的细胞行为.

主要成果

通过抑制MMSET和SETD2, H3. 3K36M突变可以减少H3K36的甲基化.
在癌症途径中,H3.3K36M细胞的改变基因表达得到了丰富.
H3.3K36M冠状细胞表现出殖民地形成的增加,细胞灭绝的抵抗力和分化缺陷.

结论

H3.3K36M蛋白重新编程了H3K36甲基化场景.
这种表观遗传重编程通过改变与癌症相关的基因表达和促进癌症细胞表型,有助于冠状腺瘤瘤发生.

基因组H3.3K36M突变重新编程了冠状细胞瘤的表观基因组

概括

科学领域

背景情况

研究的目的

主要方法

主要成果

结论

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基因组H3.3K36M突变重新编程了冠状细胞瘤的表观基因组

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概括

科学领域

背景情况

研究的目的

主要方法

主要成果

结论

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