Chromatin modifications during repair of environmental exposure-induced DNA damage: a potential mechanism for stable epigenetic alterations - PubMed (original) (raw)

Review

Chromatin modifications during repair of environmental exposure-induced DNA damage: a potential mechanism for stable epigenetic alterations

Heather M O'Hagan. Environ Mol Mutagen. 2014 Apr.

Abstract

Exposures to environmental toxicants and toxins cause epigenetic changes that likely play a role in the development of diseases associated with exposure. The mechanism behind these exposure-induced epigenetic changes is currently unknown. One commonality between most environmental exposures is that they cause DNA damage either directly or through causing an increase in reactive oxygen species, which can damage DNA. Like transcription, DNA damage repair must occur in the context of chromatin requiring both histone modifications and ATP-dependent chromatin remodeling. These chromatin changes aid in DNA damage accessibility and signaling. Several proteins and complexes involved in epigenetic silencing during both development and cancer have been found to be localized to sites of DNA damage. The chromatin-based response to DNA damage is considered a transient event, with chromatin being restored to normal as DNA damage repair is completed. However, in individuals chronically exposed to environmental toxicants or with chronic inflammatory disease, repeated DNA damage-induced chromatin rearrangement may ultimately lead to permanent epigenetic alterations. Understanding the mechanism behind exposure-induced epigenetic changes will allow us to develop strategies to prevent or reverse these changes. This review focuses on epigenetic changes and DNA damage induced by environmental exposures, the chromatin changes that occur around sites of DNA damage, and how these transient chromatin changes may lead to heritable epigenetic alterations at sites of chronic exposure.

Keywords: DNA methylation; histone modifications; reactive oxygen species; toxicants.

Copyright © 2013 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1. Model for how environmental exposure-induced DNA damage may lead to epigenetic silencing

At sites of environmental exposure, either the exposure itself or increased levels of ROS caused by exposure cause DNA damage (red star). At the sites of damage histone modifications occur (green circles) and the chromatin is remodeled. Additionally, epigenetic silencing proteins are recruited to the site of damage, possibly to prevent transcription from interfering with the repair process. It is unclear at this time if all of these proteins are being recruited to all sites of damage and whether or not they are interacting with each other. In most instances, after completion of DNA repair the chromatin is restored back to normal, the epigenetic silencing proteins are no longer localized to the area, and transcription resumes. In cases of chronic exposure, DNA damage and repair cycles can happen repeatedly and, in rare instances, the chromatin structure may not be returned to normal and binding of the epigenetic silencing proteins may persist, resulting in stable epigenetic silencing.

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References

    1. Alegria-Torres JA, Barretta F, Batres-Esquivel LE, Carrizales-Yanez L, Perez-Maldonado IN, Baccarelli A, Bertazzi PA. Epigenetic markers of exposure to polycyclic aromatic hydrocarbons in Mexican brickmakers: a pilot study. Chemosphere. 2013;91:475–480. - PubMed
    1. Aloia L, Di Stefano B, Di Croce L. Polycomb complexes in stem cells and embryonic development. Development. 2013;140:2525–2534. - PubMed
    1. Antwih DA, Gabbara KM, Lancaster WD, Ruden DM, Zielske SP. Radiation-induced epigenetic DNA methylation modification of radiation-response pathways. Epigenetics. 2013:8. - PMC - PubMed
    1. Avissar-Whiting M, Veiga KR, Uhl KM, Maccani MA, Gagne LA, Moen EL, Marsit CJ. Bisphenol A exposure leads to specific microRNA alterations in placental cells. Reprod Toxicol. 2010;29:401–406. - PMC - PubMed
    1. Aypar U, Morgan WF, Baulch JE. Radiation-induced epigenetic alterations after low and high LET irradiations. Mutat Res. 2011;707:24–33. - PubMed

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