NSD2 aggravates metabolic dysfunction-associated steatotic liver disease progression by suppressing TFEB-mediated autophagy-lysosomal pathway

Extensive research has demonstrated that impaired autophagy contributes to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Qiao et al. identified NSD2 in the liver as a novel and essential regulator of MASLD. NSD2 epigenetically represses TFEB transcription through trimethylation of histone H4 at lysine 20 (H4K20me3), thereby impairing autophagic flux to exacerbate hepatic steatosis. In conclusion, NSD2 functions as a crucial epigenetic regulator of impaired autophagic flux in the liver, offering a novel therapeutic target for MASLD management. Overall design: We conducted CUT&Tag analysis using anti-H4K20me3 antibody in control and shNsd2 human HepG2 cells.