Large-Scale Chromatin Rearrangements in Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 May 28

PMID 35625988

Authors

Kosuke Yamaguchi

Xiaoying Chen

Asami Oji

Ichiro Hiratani

Pierre-Antoine Defossez

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Yusufova N, Kloetgen A, Teater M, Osunsade A, Camarillo J, Chin C . Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture. Nature. 2020; 589(7841):299-305. PMC: 7855728. DOI: 10.1038/s41586-020-3017-y. View

Gao M, Wang J, Rousseaux S, Tan M, Pan L, Peng L . Metabolically controlled histone H4K5 acylation/acetylation ratio drives BRD4 genomic distribution. Cell Rep. 2021; 36(4):109460. DOI: 10.1016/j.celrep.2021.109460. View

Vaughan R, Kupai A, Foley C, Sagum C, Tibben B, Eden H . The histone and non-histone methyllysine reader activities of the UHRF1 tandem Tudor domain are dispensable for the propagation of aberrant DNA methylation patterning in cancer cells. Epigenetics Chromatin. 2020; 13(1):44. PMC: 7585203. DOI: 10.1186/s13072-020-00366-4. View

Caron P, Pobega E, Polo S . DNA Double-Strand Break Repair: All Roads Lead to HeterochROMAtin Marks. Front Genet. 2021; 12:730696. PMC: 8440905. DOI: 10.3389/fgene.2021.730696. View

Klein I, Boija A, Afeyan L, Hawken S, Fan M, DallAgnese A . Partitioning of cancer therapeutics in nuclear condensates. Science. 2020; 368(6497):1386-1392. PMC: 7735713. DOI: 10.1126/science.aaz4427. View

Grosselin K, Durand A, Marsolier J, Poitou A, Marangoni E, Nemati F . High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer. Nat Genet. 2019; 51(6):1060-1066. DOI: 10.1038/s41588-019-0424-9. View

Macchi F, Sadler K . Unraveling the Epigenetic Basis of Liver Development, Regeneration and Disease. Trends Genet. 2020; 36(8):587-597. DOI: 10.1016/j.tig.2020.05.002. View

Gapa L, Alfardus H, Fischle W . Unconventional metabolites in chromatin regulation. Biosci Rep. 2022; 42(1). PMC: 8777195. DOI: 10.1042/BSR20211558. View

Rousseaux S, Wang J, Khochbin S . Cancer hallmarks sustained by ectopic activations of placenta/male germline genes. Cell Cycle. 2013; 12(15):2331-2. PMC: 3841303. DOI: 10.4161/cc.25545. View

10.

Schuster-Bockler B, Lehner B . Chromatin organization is a major influence on regional mutation rates in human cancer cells. Nature. 2012; 488(7412):504-7. DOI: 10.1038/nature11273. View

11.

Kim K, Chadalapaka G, Lee S, Yamada D, Sastre-Garau X, Defossez P . Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2011; 31(8):1034-44. PMC: 3288192. DOI: 10.1038/onc.2011.296. View

12.

Zuin J, Roth G, Zhan Y, Cramard J, Redolfi J, Piskadlo E . Nonlinear control of transcription through enhancer-promoter interactions. Nature. 2022; 604(7906):571-577. PMC: 9021019. DOI: 10.1038/s41586-022-04570-y. View

13.

Phillips R, Soshnev A, Allis C . Epigenomic Reprogramming as a Driver of Malignant Glioma. Cancer Cell. 2020; 38(5):647-660. PMC: 8248764. DOI: 10.1016/j.ccell.2020.08.008. View

14.

Surdez D, Zaidi S, Grossetete S, Laud-Duval K, Ferre A, Mous L . STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma. Cancer Cell. 2021; 39(6):810-826.e9. DOI: 10.1016/j.ccell.2021.04.001. View

15.

Kong X, Chen J, Xie W, Brown S, Cai Y, Wu K . Defining UHRF1 Domains that Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties. Cancer Cell. 2019; 35(4):633-648.e7. PMC: 6521721. DOI: 10.1016/j.ccell.2019.03.003. View

16.

Nichols M, Corces V . Principles of 3D compartmentalization of the human genome. Cell Rep. 2021; 35(13):109330. PMC: 8265014. DOI: 10.1016/j.celrep.2021.109330. View

17.

Jerkovic I, Cavalli G . Understanding 3D genome organization by multidisciplinary methods. Nat Rev Mol Cell Biol. 2021; 22(8):511-528. DOI: 10.1038/s41580-021-00362-w. View

18.

Pappalardi M, Keenan K, Cockerill M, Kellner W, Stowell A, Sherk C . Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer. 2021; 2(10):1002-1017. PMC: 8594913. View

19.

Kubo N, Ishii H, Xiong X, Bianco S, Meitinger F, Hu R . Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation. Nat Struct Mol Biol. 2021; 28(2):152-161. PMC: 7913465. DOI: 10.1038/s41594-020-00539-5. View

20.

Chew G, Bleakley M, Bradley R, Malik H, Henikoff S, Molaro A . Short H2A histone variants are expressed in cancer. Nat Commun. 2021; 12(1):490. PMC: 7817690. DOI: 10.1038/s41467-020-20707-x. View