Ehmt2's transcriptional coactivation restricts glucocorticoid-induced insulin resistance in a study with male mice

Glucocorticoids play a key role in metabolic adaptation during stress, such as fasting and starvation. Excess and/or chronic glucocorticoid exposure, however, causes metabolic disorders that include insulin resistance dyslipidemia and hepatic steatosis. Glucocorticoid receptor (GR) is known to regulate a wide variety of primary target genes. However, the specificity of this regulation due to interactions with various transcriptional coactivators such as Ehmt2 remains to be further investigated. Here, we aim to identify Ehmt2 coactivation function-dependent GR primary target genes that may play a role in promoting insulin sensitivity Overall design: WT C57BL6/J male mice from Jackson laboratory were purchased as controls. Ehmt2 mutant mice (Ehmt2K182R/K182R) were generated, in which nucleotide sequences encoding lysine 182 were converted from AAA to AGG (arginine), using CRISPR knock in technology. 8 week old male mice were treated for 5 hours with 2mg/kg dexamethasone sodium phosphate (Sigma, Cleveland, OH, PHR1768)via IP injection. Livers were collected and RNA was extracted.