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ToxSci Advance Access published online on May 12, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh164
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received March 17, 2004
Accepted April 29, 2004

Review

The Role of Chromatin in Molecular Mechanisms of Toxicity

Jonathan G. Moggs 1* George Orphanides 1

1 Syngenta CTL, Alderley Park, Cheshire, SK10 4TJ, United Kingdom

* To whom correspondence should be addressed. E-mail: jonathan.moggs{at}syngenta.com.


  Abstract

Eukaryotic cells store their genetic information in the form of a highly organised nucleoprotein complex termed chromatin. The high degree of compaction of DNA within chromatin places severe constraints on proteins that require access to the DNA template to facilitate gene transcription, DNA replication and DNA repair. As a consequence, eukaryotic cells have developed sophisticated mechanisms to allow chromatin to be rapidly decompacted locally for access by DNA binding proteins. Once thought to play only a structural role, it now appears that chromatin plays a key regulatory role by marshalling access to the DNA template. Here we review the role played by chromatin in the cellular response to physiological and toxicological stimuli and describe how changes in chromatin structure may in the future be used as markers of toxicity. We also review the evidence that chromatin itself is the direct target of certain toxicants and that toxicant-induced perturbations in chromatin structure may precipitate adverse effects.

Key Words: chromatin, histone, toxicology, genome, epigenetic .


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