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Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells

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Abstract

Extensive epidemiological data indicate that inorganic arsenic is associated with several types of human cancer. Nevertheless, the underlying mechanisms are poorly understood. Among its mode of action are the alterations on DNA methylation, which provoke aberrant gene expression. However, beyond DNA methylation, little is known about arsenic’s effects on chromatin. In this study, we investigated the effects of sodium arsenite (NaAsO2) on global histone modifications and nucleosome-associated proteins. Our findings revealed that NaAsO2 exposure significantly increases global histone acetylation. This effect was related to the inhibition of histone deacetylase (HDAC) activity because NaAsO2 was able to inhibit HDACs comparable to the well-known HDAC inhibitor trichostatin A (TSA). Furthermore, analyses of the dynamic properties of the nucleosome-associated high mobility group N proteins demonstrate that NaAsO2 elevates their mobility. Thus, our data suggest that NaAsO2 induces chromatin opening by histone hyperacetylation due to HDAC inhibition and increase of the mobility of nucleosome-associated proteins. As the chromatin compaction is crucial for the regulation of gene expression as well as for genome stability, we propose that chromatin opening by NaAsO2 may play a significant role to impart its genotoxic effects.

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Acknowledgments

We thank Dr. L.A. Herrera for his comments to this manuscript and Thomas Fischer for his technical assistance. The work was supported by a graduate program (GK639) from the DFG. We thank the DAAD for grant support for T. Ramirez.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, University of Wuerzburg, Am Hubland, 97074, Wuerzburg, Germany

    Tzutzuy Ramirez, Jan Brocher & Robert Hock

  2. Institute of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg, Germany

    Tzutzuy Ramirez & Helga Stopper

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  1. Tzutzuy Ramirez
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  2. Jan Brocher
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  3. Helga Stopper
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  4. Robert Hock
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Corresponding author

Correspondence to Robert Hock.

Additional information

Communicated by T. Misteli

Tzutzuy Ramirez and Jan Brocher contributed equally.

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Ramirez, T., Brocher, J., Stopper, H. et al. Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells. Chromosoma 117, 147–157 (2008). https://doi.org/10.1007/s00412-007-0133-5

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  • DOI: https://doi.org/10.1007/s00412-007-0133-5

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