Set7 as a histone lysine methyltransferase is a hyperglycemic sensor involved in the persistent activation of inflammatory genes. Set7 mediated lysine methylation also regulates reactive oxidative species (ROS) signaling implicated in the pathogenesis of diabetic complications. While we have defined the role of Set7 enzyme in epigenetic regulation that links hyperglycemia with histone modifications, much less is known about its non-coding RNA. We have discovered the antisense transcript of Set7 (ASSET) is expressed in the vasculature. Expression of sense Set7 and ASSET in response to ROS-dependent stimulus was determined in mouse smooth muscle cells by RT-qPCR. While H₂O₂ did not alter sense Set7 mRNA expression, we observe significant upregulation of ASSET. ROS scavengers attenuate the expression of ASSET. Furthermore, pharmacological HDAC inhibition studies combined with experimental results using the histone acetyltransferase inhibitor C646, suggest an important role for histone acetylation in the regulation of ASSET expression. We hypothesize ASSET plays a primary regulatory role in response to oxidative stress and this could represent a novel mechanism of gene regulation conferred by diabetes-induced oxidant redox signaling