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.
Front Med. 2019 Jun;13(3):289-297. doi: 10.1007/s11684-018-0667-3. Epub 2019 Jun 11.
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.
恶性细胞转化可以被认为是一系列由致癌转录因子和上游信号通路驱动的细胞重编程事件。染色质的可塑性和动力学是控制细胞重编程的关键决定因素。因此，染色质动力学的增加可能是驱动致癌作用和产生肿瘤细胞异质性的一个必要步骤，而肿瘤细胞异质性对于选择侵袭性特性是必不可少的，包括细胞扩散的能力和对治疗的耐药性。组蛋白的供应和剂量以及组蛋白变体是染色质动力学的最佳调控因子。通过促进细胞重编程，组蛋白剂量不足和组蛋白变体也应该在细胞转化和肿瘤转移中起着至关重要的作用。在这里，我们总结并讨论了我们对组蛋白供应和组蛋白变体在染色质动力学中的作用及其增强致癌细胞重编程和肿瘤异质性的能力的认识。
