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2019, Volume 13, Issue 3

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Frontiers of Medicine >> 2019, Volume 13, Issue 3 doi: 10.1007/s11684-018-0667-3

Histone variants: critical determinants in tumour heterogeneity

. CNRS UMR 5309, Inserm, U1209, University of Grenoble Alpes, Institute for Advanced Biosciences, 38706, Grenoble, France.. State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Accepted: 2018-10-09 Available online: 2018-10-09
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Abstract

Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

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