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Chromatin remodeling by polyamines and polyamine analogs

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Abstract

Natural polyamines are involved in many molecular processes, including maintenance of DNA structure and RNA processing and translation. Our aim here is to present an overview of the literature concerning the significance of polyamines in the modulation of chromatin arrangement and the transcriptional regulation of gene expression. The pleiotropic picture emerging from the published data highlights that these polycations take part in apparently diverging effects, possibly depending on the heterogeneous experimental settings described, and on a methodological approach aimed at the evaluation of the global levels of the histone chemical modifications. Since the relevant changes observed appear to be rather local and gene specific, investigating histone modifications at the level of specific gene promoters of interest is thus to be recommended for future studies. Furthermore, decoding the multiple regulatory mechanisms by which polyamines exert their influence on chromatin-modifier enzymes will reasonably require focus on selected individual polyamine-regulated genes. The evaluation of the many known chromatin-remodeling enzymes for their individual susceptibility to polyamines or polyamine derivatives will also be helpful: determining how they discriminate between the different enzyme isoforms is expected to be a fruitful line of research for drug discovery, e.g., in cancer prevention and therapy. Indeed, polyamine derivatives acting as epigenetic modulators appear to be molecules with great potential as antitumor drugs. All these novel polyamine-based pharmacologically active molecules are thus promising tools, both as a stand-alone strategy and in combination with other anticancer compounds.

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Abbreviations

ChIP:

Chromatin immunoprecipitation

CpG:

Cytosine preceding guanine

DFMO:

α-Difluoromethylornithine

HATs:

Histone acetyltransferases

HDACs:

Histone deacetylases

HDACi:

Histone deacetylase inhibitor

LSD1:

Lysine demethylase 1

ODC:

Ornithine decarboxylase

PABA:

Polyaminobenzamide derivatives

PAHA:

Polyaminohydroxamic acid derivatives

PAOs:

Polyamine oxidases

PcG:

Polycomb group

PUT:

Putrescine

SAHA:

Suberoylanilide hydroxamic acid

SAM:

S-adenosylmethionine

SC:

Stem cell

SMO:

Spermine oxidase

SPD:

Spermidine

SPM:

Spermine

TGase:

Transglutaminase

TrxG:

Thritorax group

TSGs:

Tumor suppressor genes

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Acknowledgments

AP thanks the National Institute for Cardiovascular Research [(INRC), Bologna, Italy] for the past, and the IRCCS Romagnolo Scientific Institute for the Study and Treatment of Cancer [(IRST), Meldola, Italy] for the present, granting of funding to partially cover her fellowship.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cellular and Molecular Engineering “S. Cavalcanti”, Department of Electrical, Electronic and Information Engineering “G. Marconi” (DEI), University of Bologna, via Venezia 52, 47521, Cesena (FC), Italy

    Alice Pasini & Emanuele Giordano

  2. National Institute for Cardiovascular Research (INRC), University of Bologna, via Irnerio 48, 40126, Bologna (BO), Italy

    Claudio M. Caldarera & Emanuele Giordano

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  1. Alice Pasini
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  2. Claudio M. Caldarera
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  3. Emanuele Giordano
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Correspondence to Emanuele Giordano.

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Pasini, A., Caldarera, C.M. & Giordano, E. Chromatin remodeling by polyamines and polyamine analogs. Amino Acids 46, 595–603 (2014). https://doi.org/10.1007/s00726-013-1550-9

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