Involvement of insulin-induced reversible chromatin remodeling in altering the expression of oxidative stress-responsive genes under hyperglycemia in 3T3-L1 preadipocytes

The epigenetic control mechanisms, regulating insulin-induced oxidative stress generation, under hyperglycemic condition are yet to be elucidated. We set out to assess the role of chromatin regulatory factors in regulating the transcription of genes that are critical for mediating oxidative stress response under hyperglycemic/hyperinsulinemic condition. Our results outline a significant increase in the ROS generation accompanied by a decrease in the histone H3 acetylation, H3 Ser-10 phosphorylation, H3K4 methylation and an increase in the H3K9 methylation, after 30 min of insulin treatment under hyperglycemic condition. However, after 12 h of insulin treatment a reversal of these histone H3 modifications was observed which commensurate with the reduced ROS generation. Microarray data revealed that the expression of stress responsive genes (Hsp90, Hspd1, DnajC15, Hsf5 and Mapk3) decreased after12 h of insulin treatment, after an initial increase at 30 min. We observed the direct regulation of these stress responsive genes by reversible histone modifications under hyperglycemic/hyperinsulinemic condition at both time intervals. Further, pre-incubation with catalase attenuates these changes. To the best of our knowledge this is the first report that shows the role of reversible histone modifications in regulating oxidative stress-responsive genes under hyperglycemic condition in 3T3-L1 preadipocytes.

► Increased ROS generation under hyperglycemic/hyperinsulinemic condition
► H3-Ac, H3-p and H3K4me were decreased and H3K9me level was increased.
► However, after 12 h of insulin treatment a reversal of these changes was seen.
► Microarray shows differential expression of stress responsive genes.
► ChIP-RT-PCR shows regulation of stress responsive genes by histone modifications.