Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation
Year: 2016
Type: article
Abstract: Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone variants provides a first step toward an understanding of the functional significance of the diversity of histone structures, especially in inorganic arsenic-mediated gene expression and carcinogenesis.
Source: Molecular & Cellular Proteomics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: National Science Foundation, Florida State University, National High Magnetic Field Laboratory, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Cancer Institute, National Institute of Environmental Health Sciences, Division of Materials Research, High Magnetic Field Laboratory, Chinese Academy of Sciences, State of Florida
Awards: G2294341347, G2386482098, G4079872414, G4624992917, G502626589, National High Magnetic Field Laboratory Renewal 2013-2017, An Investigation into the Novel Role of PARP1 in Co-transcriptional Splicing, The role of chromatin structural and epigenetic changes in arsenic-induced gene expression, Interdisciplinary Research Training in Cancer Biology
OpenAlex ID: W2350638789