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Epigenetic Basis of Cellular Senescence and Its Implications in Aging
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Genes 2017, 8(12), 367; doi:10.3390/genes8120367

Histone MacroH2A1: A Chromatin Point of Intersection between Fasting, Senescence and Cellular Regeneration

1
Center for Translational Medicine, International Clinical Research Center, St’Anne University Hospital, Brno 656 91, Czech Republic
2
Faculty of Medicine, Masaryk University, Brno 656 91, Czech Republic
3
Division of Medicine, Institute for Liver and Digestive Health, University College London (UCL), London WC1E 6BT, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Jessica K. Tyler
Received: 26 October 2017 / Revised: 27 November 2017 / Accepted: 30 November 2017 / Published: 5 December 2017
(This article belongs to the Special Issue The Epigenetics of Aging and Longevity)
View Full-Text   |   Download PDF [1077 KB, uploaded 5 December 2017]   |  

Abstract

Histone variants confer chromatin unique properties. They have specific genomic distribution, regulated by specific deposition and removal machineries. Histone variants, mostly of canonical histones H2A, H2B and H3, have important roles in early embryonic development, in lineage commitment of stem cells, in the converse process of somatic cell reprogramming to pluripotency and, in some cases, in the modulation of animal aging and life span. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Furthermore, macroH2A1 participates in the formation of senescence-associated heterochromatic foci (SAHF) in senescent cells, and multiple lines of evidence in genetically modified mice suggest that macroH2A1 integrates nutritional cues from the extracellular environment to transcriptional programs. Here, we review current molecular evidence based on next generation sequencing data, cell assays and in vivo models supporting different mechanisms that could mediate the function of macroH2A1 in health span and life span. We will further discuss context-dependent and isoform-specific functions. The aim of this review is to provide guidance to assess histone variant macroH2A1 potential as a therapeutic intervention point. View Full-Text
Keywords: histone variant macroH2A1; fasting; senescence; regeneration histone variant macroH2A1; fasting; senescence; regeneration
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lo Re, O.; Vinciguerra, M. Histone MacroH2A1: A Chromatin Point of Intersection between Fasting, Senescence and Cellular Regeneration. Genes 2017, 8, 367.

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