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Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation and the epigenome of senescent cells

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Abstract

Senescence is a stable proliferation arrest characterized by profound changes in cellular morphology and metabolism as well as by extensive chromatin reorganization in the nucleus. One particular hallmark of chromatin changes during senescence is the formation of punctate DNA foci in DAPI-stained senescent cells that have been called senescence-associated heterochromatin foci (SAHF). While many advances have been made concerning our understanding of the effectors of senescence, how chromatin is reorganized and maintained in senescent cells has remained largely elusive. Because chromatin structure is inherently dynamic, senescent cells face the challenge of developing chromatin maintenance mechanisms in the absence of DNA replication in order to maintain the senescent phenotype. Here, we summarize and review recent findings shedding light on SAHF composition and formation via spatial repositioning of chromatin, with a specific focus on the role of lamin B1 for this process. In addition, we discuss the physiological implication of SAHF formation, the role of histone variants, and histone chaperones during senescence and also elaborate on the more general changes observed in the epigenome of the senescent cells.

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Abbreviations

ATRX:

Alpha-thalassemia/mental retardation X-linked

DAXX:

Death-domain associated protein

HP1:

Heterochromatin protein 1

H3K9me3:

Histone H3 trimethylated at lysine 9

OIS:

Oncogene-induced senescence

PML:

Promyelocytic leukemia

PML-NBs:

PML nuclear bodies

SAHF:

Senescence-associated heterochromatin foci

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Acknowledgments

We thank all members of the Department of Gynecology of the University Hospital Zürich for the help and discussion. We apologize to the authors whose work could not be cited owing to space limitations. This work was supported by grants from the Swiss National Foundation (project grant 31003A-127450 to MS and Marie-Heim Vögtlin grant PMPDP3_139706 to AC) and by the Kanton of Zürich.

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The authors declare that they have no conflict of interest.

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  1. Department of Gynecology, University Hospital Zürich, Wagistrasse 14, 8952, Schlieren, Switzerland

    Armelle Corpet & Manuel Stucki

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  1. Armelle Corpet
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Correspondence to Manuel Stucki.

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Corpet, A., Stucki, M. Chromatin maintenance and dynamics in senescence: a spotlight on SAHF formation and the epigenome of senescent cells. Chromosoma 123, 423–436 (2014). https://doi.org/10.1007/s00412-014-0469-6

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