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dc.contributor.authorAnderson, AM
dc.contributor.authorCarter, KW
dc.contributor.authorAnderson, D
dc.contributor.authorWise, MJ
dc.date.accessioned2020-12-21T01:48:08Z
dc.date.available2020-12-21T01:48:08Z
dc.date.issued2012
dc.identifierpii: PONE-D-11-22637
dc.identifier.citationAnderson, A. M., Carter, K. W., Anderson, D. & Wise, M. J. (2012). Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.. PLoS One, 7 (4), pp.e34158-. https://doi.org/10.1371/journal.pone.0034158.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/256665
dc.description.abstractBACKGROUND: 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 mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleCoexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0034158
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume7
melbourne.source.issue4
melbourne.source.pagese34158-
dc.rights.licenseCC BY
melbourne.elementsid1101505
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319570
melbourne.contributor.authorAnderson, Alison
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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