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BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning

ABSTRACT: 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 found that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensible role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility for key thermogenic genes in close proximity to PPARg and EBF2 binding sites. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE128747 | GEO | 2020/02/20

REPOSITORIES: GEO

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Transcriptome analysis in adipose tissues of BAF60a knockout mice

Project description: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. BAF60a serves an indispensable role in cold-induced thermogenesis in brown fat. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced browning of inguinal white adipose tissue. These results suggest a dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs. To elucidate the mechanism, we performed microarray annalysis in inguinal white adipose tissues from mice after chronic cold exposure.

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