A Functionally Conserved Enhancer is Critical for PGC1A Expression and Thermogenesis in Brown Fat - PubMed
4 hours ago
- #brown adipose tissue
- #PGC1A
- #thermogenesis
- Brown adipose tissue (BAT) undergoes age-related involution into white adipose tissue (WAT), with unclear epigenetic mechanisms.
- Study investigates transcriptomic dynamics of goat perirenal adipose tissue (PRAT) across postnatal stages, profiling active histone modifications and chromatin accessibility.
- PRAT whitening correlates with reduced active histone marks and decreased chromatin accessibility at thermogenesis and mitochondrial function genes.
- Two BAT-specific active enhancers, PGC1A-En1 and PGC1A-En2, identified with additive effects and activation under cold stimulation.
- Functional repression of PGC1A-En1 and/or PGC1A-En2 reduces PGC1A expression and impairs thermogenic capacity in goat brown adipocytes.
- Mouse Pgc1a-En1 repression in vivo decreases Pgc1a expression and attenuates cold-induced thermogenesis in BAT.
- Conserved PGC1A-hEn1 is critical for PGC1A expression and thermogenic activation in human brown adipocytes.
- Findings highlight conserved enhancer elements as potential therapeutic targets for metabolic disorders.