Frontiers of Medicine

, Volume 13, Issue 3, pp 289–297 | Cite as

Histone variants: critical determinants in tumour heterogeneity

  • Tao Wang
  • Florent Chuffart
  • Ekaterina Bourova-Flin
  • Jin Wang
  • Jianqing Mi
  • Sophie Rousseaux
  • Saadi KhochbinEmail author
Open Access


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.


cancer-testis TH2B TH2A H1T H1.0 H1F0 linker histones 



This review was prepared in frame of “Pitcher” research program on tumour heterogeneity (Plan Cancer: No. C16012CS). WT is a postdoctoral fellow on this program. Research in SK and JM is supported by Cai Yuanpei program and by the “Pôle Sino-Français des Sciences du Vivant et Genomique.”

SK laboratory is also supported by a grant from “Foundation pour la Recherche Medicale (FRM)” “analyse bio-informatique pour la recherche en biologie” program, as well as by ANR Episperm3 program. Additional support is from: the “Université Grenoble Alpes” ANR-15-IDEX-02 LIFE and SYMER programs as well as from Fondation ARC “Canc’air” project (No. RAC16042CLA), Plan Cancer (No. CH7-INS15B66).


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© The Author(s) 2018

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the appropriate credit is given to the original author(s) and the source, and a link is provided to the Creative Commons license, which indicates if changes are made.

Authors and Affiliations

  • Tao Wang
    • 1
    • 2
  • Florent Chuffart
    • 1
  • Ekaterina Bourova-Flin
    • 1
  • Jin Wang
    • 2
  • Jianqing Mi
    • 2
  • Sophie Rousseaux
    • 1
  • Saadi Khochbin
    • 1
    Email author
  1. 1.CNRS UMR 5309, Inserm, U1209University of Grenoble Alpes, Institute for Advanced BiosciencesGrenobleFrance
  2. 2.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 GenomiqueRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

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