Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer |
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| Authors: | Subhadip Kundu MD Ray Ashok Sharma |
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| Institution: | 1. Laboratory of Chromatin and Cancer Epigenetics, Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India;2. Department of Surgical Oncology, IRCH, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India;1. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium;2. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium;1. Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;2. The Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China;3. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;4. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan;5. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310058, China;6. MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China;1. Nevada Genomics Center, Reno, NV 89557, USA;2. University of Nevada, Reno, Reno, NV 89557, USA;3. Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USA;4. Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;5. Theiagen Consulting, LLC, Highlands Ranch, CO 80128, USA;6. Nevada Center for Bioinformatics, Reno, NV 89557, USA;7. Nevada State Public Health Laboratory, Reno, NV 89503, USA;8. Southern Nevada Public Health Laboratory of the Southern Nevada Health District, Las Vegas, NV 89107, USA;1. National Key Laboratory of Plant Molecular Genetics, CAS Centre for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China;2. University of the Chinese Academy of Sciences, Beijing 100049, China;3. School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China |
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| Abstract: | In eukaryotic genome biology, the genomic organization inside the three-dimensional(3 D) nucleus is highly complex, and whether this organization governs gene expression is poorly understood. Nuclear lamina(NL)is a filamentous meshwork of proteins present at the lining of inner nuclear membrane that serves as an anchoring platform for genome organization. Large chromatin domains termed as lamina-associated domains(LADs), play a major role in silencing genes at the nuclear periphery. The interaction of the NL and genome is dynamic and stochastic. Furthermore, many genes change their positions during developmental processes or under disease conditions such as cancer, to activate certain sorts of genes and/or silence others. Pericentromeric heterochromatin(PCH) is mostly in the silenced region within the genome, which localizes at the nuclear periphery. Studies show that several genes located at the PCH are aberrantly expressed in cancer. The interesting question is that despite being localized in the pericentromeric region,how these genes still manage to overcome pericentromeric repression. Although epigenetic mechanisms control the expression of the pericentromeric region, recent studies about genome organization and genome-nuclear lamina interaction have shed light on a new aspect of pericentromeric gene regulation through a complex and coordinated interplay between epigenomic remodeling and genomic organization in cancer. |
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| Keywords: | LADs Pericentromere Heterochromatin Gene regulation Epigenetics Cancer Genome organization |
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