The Role of MacroH2A Histone Variants in Cancer
Por:
Hsu, CJ, Meers, O, Buschbeck, M and Heidel, FH
Publicada:
1 jun 2021
Ahead of Print:
15 jun 2021
Resumen:
Simple Summary The structural unit of chromatin is the nucleosome that is composed of DNA wrapped around a core of eight histone proteins. Histone variants can replace 'standard' histones at specific sites of the genome. Thus, histone variants modulate all functions in the context of chromatin, such as gene expression. Here, we provide a concise review on a group of histone variants termed macroH2A. They contain two additional domains that contribute to their increased size. We discuss how these domains mediate molecular functions in normal cells and the role of macroH2As in gene expression and cancer. The epigenome regulates gene expression and provides a molecular memory of cellular events. A growing body of evidence has highlighted the importance of epigenetic regulation in physiological tissue homeostasis and malignant transformation. Among epigenetic mechanisms, the replacement of replication-coupled histones with histone variants is the least understood. Due to differences in protein sequence and genomic distribution, histone variants contribute to the plasticity of the epigenome. Here, we focus on the family of macroH2A histone variants that are particular in having a tripartite structure consisting of a histone fold, an intrinsically disordered linker and a globular macrodomain. We discuss how these domains mediate different molecular functions related to chromatin architecture, transcription and DNA repair. Dysregulated expression of macroH2A histone variants has been observed in different subtypes of cancer and has variable prognostic impact, depending on cellular context and molecular background. We aim to provide a concise review regarding the context- and isoform-dependent contributions of macroH2A histone variants to cancer development and progression.
Filiaciones:
Hsu, CJ:
Greifswald Univ Med, Internal Med C, D-17475 Greifswald, Germany
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukaemia Epigenet & Biol Program, Campus Can Ruti, Badalona 08916, Spain
Germans Trias & Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Campus Can Ruti, Badalona 08916, Spain
Heidel, FH:
Greifswald Univ Med, Internal Med C, D-17475 Greifswald, Germany
Fritz Lipmann Inst, Leibniz Inst Aging, D-07745 Jena, Germany
Green Published, gold
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