Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.

ABSTRACT: Altered nitric oxide (•NO) metabolism underlies cancer pathology, but mechanisms explaining many •NO-associated phenotypes remain unclear. We have found that cellular exposure to •NO changes histone posttranslational modifications (PTM) by directly inhibiting the catalytic activity of JmjC-domain containing histone demethylases. Herein, we describe how •NO exposure links modulation of histone PTMs to gene expression changes that promote oncogenesis. Through high-resolution mass spectrometry, we generated an extensive map of •NO-mediated histone PTM changes at 15 critical lysine residues on the core histones H3 and H4. Concomitant microarray analysis demonstrated that exposure to physiologic •NO resulted in the differential expression of over 6,500 genes in breast cancer cells. Measurements

SUBMITTER: Vasudevan D 

PROVIDER: S-EPMC4681644 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature