coexpression of nuclear receptors and histone methylation modifying genes in the testis implications for endocrine disruptor modes of actioncoexpression核受体和组蛋白甲基化修饰基因影响睾丸的内分泌干扰模式的行动.pdf

Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action 1 2 2 3 Alison M. Anderson *, Kim W. Carter , Denise Anderson , Michael J. Wise 1 Computer Science and Software Engineering, University of Western Australia, Perth, Australia, 2 Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia, 3 Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Australia Abstract Background: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. Methodology/Principal Findings: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechan