Intestinal NSD2 aggravates hepatic steatosis during obesity through histone modifications [CUT&Tag]

The impairment of the intestinal barrier will lead to the accumulation of fat and harmful substances in the liver, inducing hepatic steatosis or steatohepatitis. Zhang et al. identified NSD2 in the intestine as a novel and essential regulator of hepatic steatosis. NSD2 directly regulates transcriptional activation of ERN1 through the modification of H3 dimethylated on lysine 36 (H3K4me36), thereby activating the ERN1-JNK axis to induce inflammatory response, intestinal barrier impairment, and hepatic steatosis. This functional mechanism of NSD2 provides a potential therapeutic target for this disease. Overall design: After 16 weeks of HFCD in NSD2fl/fl mouse and NSD2?IE mouse, colon tissues were taken and subjected to CUT & Tag assays for H3K36me2