Arsenic alters global histone modifications in lymphocytes in vitro and in vivo
| Autor: | Karin Broberg, Maria Kippler, Angeliki Pournara, Teresa Holmlund, Annika E. Wallberg, Rebecca Ceder, Roland C. Grafström, Marie Vahter |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
DNA (Cytosine-5-)-Methyltransferase 1 inorganic chemicals 0301 basic medicine Health Toxicology and Mutagenesis Arsenic biochemistry Histone Deacetylase 2 chemistry.chemical_element Biology Toxicology Arsenic Epigenesis Genetic Histones Jurkat Cells Young Adult 03 medical and health sciences chemistry.chemical_compound Proliferating Cell Nuclear Antigen Humans Histone code DNA (Cytosine-5-)-Methyltransferases Gene Silencing Lymphocytes Epigenetics Carcinogen integumentary system Histone deacetylase 2 Drinking Water Cell Biology Middle Aged Cell biology DNA-Binding Proteins Histone Code HEK293 Cells 030104 developmental biology Histone Biochemistry chemistry biology.protein Female Protein Processing Post-Translational Transcription Factors Toxicant |
| Zdroj: | Cell Biology and Toxicology. 32:275-284 |
| ISSN: | 1573-6822 0742-2091 |
| DOI: | 10.1007/s10565-016-9334-0 |
| Popis: | Arsenic, an established carcinogen and toxicant, occurs in drinking water and food and affects millions of people worldwide. Arsenic appears to interfere with gene expression through epigenetic processes, such as DNA methylation and post-translational histone modifications. We investigated the effects of arsenic on histone residues in vivo as well as in vitro. Analysis of H3K9Ac and H3K9me3 in CD4+ and CD8+ sorted blood cells from individuals exposed to arsenic through drinking water in the Argentinean Andes showed a significant decrease in global H3K9me3 in CD4+ cells, but not CD8+ cells, with increasing arsenic exposure. In vitro studies of inorganic arsenic-treated T lymphocytes (Jurkat and CCRF-CEM, 0.1, 1, and 100 μg/L) showed arsenic-related modifications of H3K9Ac and changes in the levels of the histone deacetylating enzyme HDAC2 at very low arsenic concentrations. Further, in vitro exposure of kidney HEK293 cells to arsenic (1 and 5 μM) altered the protein levels of PCNA and DNMT1, parts of a gene expression repressor complex, as well as MAML1. MAML1 co-localized and interacted with components of this complex in HEK293 cells, and in silico studies indicated that MAML1 expression correlate with HDAC2 and DNMT1 expression in kidney cells. In conclusion, our data suggest that arsenic exposure may lead to changes in the global levels of H3K9me3 and H3K9Ac in lymphocytes. Also, we show that arsenic exposure affects the expression of PCNA and DNMT1-proteins that are part of a gene expression silencing complex. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink