Nelfb Promotes Dermal White Adipose Tissue Formation Through RNA Polymerase II Mediated Adipogenic Gene Regulation

The study investigates the role of the transcriptional pause factor Nelfb in the formation of dermal white adipose tissue (dWAT), which is essential for skin functions like hair follicle regeneration and wound healing. In mice, deletion of Nelfb in preadipocyte lineages resulted in the failure of dWAT formation, perinatal lethality, and reduced expression of adipogenic genes. Nelfb facilitates an open chromatin structure and stabilizes RNA Polymerase II binding to key genes necessary for adipocyte differentiation. Restoration of adipocyte differentiation was achieved by expressing Pparg in Nelfb-depleted cells or treating Nelfb-deleted mice with the Pparg agonist rosiglitazone, which also extended their lifespan. This highlights Nelfb's critical role in regulating adipogenic gene expression for dWAT formation.