Large-Scale Chromatin Rearrangements in Cancer

Kosuke Yamaguchi; Xiaoying Chen; Asami Oji; Ichiro Hiratani; Pierre-Antoine Defossez

doi:10.3390/cancers14102384

Large-Scale Chromatin Rearrangements in Cancer

Cancers (Basel). 2022 May 12;14(10):2384. doi: 10.3390/cancers14102384.

Authors

Kosuke Yamaguchi¹, Xiaoying Chen¹, Asami Oji², Ichiro Hiratani², Pierre-Antoine Defossez¹

Affiliations

¹ UMR7216 Epigenetics and Cell Fate, Université Paris Cité, CNRS, F-75006 Paris, France.
² RIKEN Center for Biosystems Dynamics Research (RIKEN BDR), Kobe 650-0047, Japan.

Abstract

Epigenetic abnormalities are extremely widespread in cancer. Some of them are mere consequences of transformation, but some actively contribute to cancer initiation and progression; they provide powerful new biological markers, as well as new targets for therapies. In this review, we examine the recent literature and focus on one particular aspect of epigenome deregulation: large-scale chromatin changes, causing global changes of DNA methylation or histone modifications. After a brief overview of the one-dimension (1D) and three-dimension (3D) epigenome in healthy cells and of its homeostasis mechanisms, we use selected examples to describe how many different events (mutations, changes in metabolism, and infections) can cause profound changes to the epigenome and fuel cancer. We then present the consequences for therapies and briefly discuss the role of single-cell approaches for the future progress of the field.

Keywords: chromatin; epigenetics; genome organization; transformation.

Publication types

Review

Grants and funding

Research in the lab of PAD was funded by Agence Nationale de la Recherche, grant number PRCI INTEGER ANR-19-CE12-0030-01 and PRC REMEDY ANR-21-CE12-0015; by Fondation ARC (Programme Labellisé PGA1/RF20180206807); by LabEx “Who Am I?” (ANR-11-LABX-0071), Université de Paris IdEx (ANR-18-IDEX-0001) funded by the French Government through its “Investments for the Future” program; and by Fondation pour la Recherche Médicale. KY was the recipient of a postdoctoral fellowship from Fondation Association pour la Recherche sur le Cancer, and of a subsequent postdoc fellowship from Labex “Who Am I?”. This work was also supported by the Special Postdoctoral Researcher (SPDR) Program of RIKEN to A.O. and by RIKEN BDR intramural grants, RIKEN Pioneering Project ‘Genome Building from TADs’, JST CREST Grant Number JPMJCR20S5, MEXT KAKENHI Grant Number 18H05530, and JSPS KAKENHI Grant Number 20K20582 to I.H. We apologize to authors whose primary references we could not cite because of space limitations.