BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning.
Tongyu LiuLin MiJing XiongPeter OrchardQi YuLei YuXu-Yun ZhaoZhuo-Xian MengStephen C J ParkerJiandie D LinSiming LiPublished in: Nature communications (2020)
Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
Keyphrases
- adipose tissue
- genome wide
- transcription factor
- gene expression
- insulin resistance
- dna damage
- dna methylation
- high fat diet
- copy number
- genome wide identification
- high fat diet induced
- diabetic rats
- high glucose
- poor prognosis
- type diabetes
- oxidative stress
- drug induced
- public health
- metabolic syndrome
- signaling pathway
- hydrogen peroxide
- quality improvement
- fatty acid
- heat shock
- radical prostatectomy
- smoking cessation