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Histone variants: emerging players in cancer biology

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Abstract

Histone variants are key players in shaping chromatin structure, and, thus, in regulating fundamental cellular processes such as chromosome segregation and gene expression. Emerging evidence points towards a role for histone variants in contributing to tumor progression, and, recently, the first cancer-associated mutation in a histone variant-encoding gene was reported. In addition, genetic alterations of the histone chaperones that specifically regulate chromatin incorporation of histone variants are rapidly being uncovered in numerous cancers. Collectively, these findings implicate histone variants as potential drivers of cancer initiation and/or progression, and, therefore, targeting histone deposition or the chromatin remodeling machinery may be of therapeutic value. Here, we review the mammalian histone variants of the H2A and H3 families in their respective cellular functions, and their involvement in tumor biology.

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Abbreviations

ChIP:

Chromatin ImmunoPrecipitation

DDR:

DNA Damage Response

DSB:

Double-Strand Break

ESC:

Embryonic Stem Cell

HFD:

Histone Fold Domain

IF:

ImmunoFluorescence

OIS:

Oncogene-Induced Senescence

PTM:

Post-Translational Modification

TF:

Transcription Factor

TSS:

Transcription Start Site

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Acknowledgments

The authors thank Zulekha Qadeer and Alexandre Gaspar-Maia for critically reading this manuscript. The authors thank Matthew O’Connell for microscopy assistance and Pablo DeIoannes for assistance with in silico homology modeling. This work is supported by an NCI T32-CA078207 to L.F.D, a Melanoma Research Development Award (Department of Dermatology, Mount Sinai) to C.V., and The Ellison Medical Foundation New Scholar Award, Association for International Cancer Research, Hirschl/Weill-Caulier Research Award and NCI/NIH R01CA154683 to E.B.

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  1. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA

    Chiara Vardabasso, Dan Hasson, Kajan Ratnakumar, Chi-Yeh Chung, Luis F. Duarte & Emily Bernstein

  2. Department of Dermatology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA

    Chiara Vardabasso, Luis F. Duarte & Emily Bernstein

  3. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA

    Dan Hasson, Kajan Ratnakumar, Chi-Yeh Chung & Luis F. Duarte

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  1. Chiara Vardabasso
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Correspondence to Emily Bernstein.

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Vardabasso, C., Hasson, D., Ratnakumar, K. et al. Histone variants: emerging players in cancer biology. Cell. Mol. Life Sci. 71, 379–404 (2014). https://doi.org/10.1007/s00018-013-1343-z

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  • DOI: https://doi.org/10.1007/s00018-013-1343-z

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