Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells
Protein Synthesis Inhibitors
0301 basic medicine
Cell Death
Arsenites
DNA Methylation
Hydroxamic Acids
Models, Biological
Sodium Compounds
Chromatin
Histone Deacetylases
Cell Line
Nucleosomes
Histones
03 medical and health sciences
Microscopy, Fluorescence
Cell Line, Tumor
HMGN Proteins
Humans
DOI:
10.1007/s00412-007-0133-5
Publication Date:
2007-11-12T08:27:47Z
AUTHORS (4)
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 (NaAsO(2)) on global histone modifications and nucleosome-associated proteins. Our findings revealed that NaAsO(2) exposure significantly increases global histone acetylation. This effect was related to the inhibition of histone deacetylase (HDAC) activity because NaAsO(2) 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 NaAsO(2) elevates their mobility. Thus, our data suggest that NaAsO(2) 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 NaAsO(2) may play a significant role to impart its genotoxic effects.
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