NDLI: Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation*

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Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation*

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Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation*

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Rea, Matthew Jiang, Tingting Eleazer, Rebekah Eckstein, Meredith Marshall, Alan G. Fondufe-Mittendorf, Yvonne N.
Description	Author Affiliation: Rea M ( From the Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536); Jiang T ( §Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306); Eleazer R ( From the Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536); Eckstein M ( From the Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536); Marshall AG ( §Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306); Fondufe-Mittendorf YN ( From the Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536)
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.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
Journal	Molecular & Cellular Proteomics
Issue Number	7
Volume Number	15
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2016-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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