Show simple item record

dc.contributor.authorHickok, Jason R.
dc.contributor.authorVasudevan, Divya
dc.contributor.authorAntholine, William E.
dc.contributor.authorThomas, Douglas D.
dc.date.accessioned2014-01-03T17:09:33Z
dc.date.available2014-05-04T09:30:23Z
dc.date.issued2013-05
dc.identifier.bibliographicCitationHickok JR, Vasudevan D, Antholine WE, Thomas DD. Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain-containing demethylases.Journal of Biological Chemistry. 2013 May 31;288(22):16004-15. doi: 10.1074/jbc.M112.432294.en_US
dc.identifier.issn1083-351X
dc.identifier.urihttp://hdl.handle.net/10027/10988
dc.descriptionThis research was originally published in Journal of Biological Chemistry. Hickok JR, Vasudevan D, Antholine WE, Thomas DD. Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain-containing demethylases. J Biol Chem. 2013 May 31;288(22):16004-15. © the American Society for Biochemistry and Molecular Biologyen_US
dc.description.abstractMethylation of lysine residues on histone tails is an important epigenetic modification that is dynamically regulated through the combined effects of methyltransferases and demethylases. The Jumonji C domain Fe(II) α-ketoglutarate family of proteins performs the majority of histone demethylation. We demonstrate that nitric oxide ((•)NO) directly inhibits the activity of the demethylase KDM3A by forming a nitrosyliron complex in the catalytic pocket. Exposing cells to either chemical or cellular sources of (•)NO resulted in a significant increase in dimethyl Lys-9 on histone 3 (H3K9me2), the preferred substrate for KDM3A. G9a, the primary methyltransferase acting on H3K9me2, was down-regulated in response to (•)NO, and changes in methylation state could not be accounted for by methylation in general. Furthermore, cellular iron sequestration via dinitrosyliron complex formation correlated with increased methylation. The mRNA of several histone demethylases and methyltransferases was also differentially regulated in response to (•)NO. Taken together, these data reveal three novel and distinct mechanisms whereby (•)NO can affect histone methylation as follows: direct inhibition of Jumonji C demethylase activity, reduction in iron cofactor availability, and regulation of expression of methyl-modifying enzymes. This model of (•)NO as an epigenetic modulator provides a novel explanation for nonclassical gene regulation by (•)NO.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.subjectCell Biologyen_US
dc.subjectdemethylasesen_US
dc.subjectmethyltransferasesen_US
dc.subjectepigeneticsen_US
dc.titleNitric oxide modifies global histone methylation by inhibiting Jumonji C domain containing demethylasesen_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record