The H3K27 acetyltransferase p300 is dispensable for thermogenic adipose tissue formation and function

Abstract

AbstractBrown adipose tissue (BAT) is specialized for thermogenesis because it contains uncoupling protein (UCP)-1. BAT is also an endocrine organ, producing many signalling molecules important for regulating the metabolism of peripheral organs. Mounting evidence suggest that histone modifying enzymes are integral for the development, tissue maintenance, and postnatal functioning of brown and beige adipocytes. p300 and its functional homologue CREB-binding protein (CBP) are histone acetyltransferases that form the transcriptionally activating histone 3 acetyl-lysine 27 (H3K27ac) mark. UsingUcp1-Cre, we examined the requirement of p300 activity specifically within thermogenic adipocytes. We hypothesized that loss of p300 activity would impair gene programming integral for BAT development/function, rendering knockouts susceptible to metabolic dysfunction and unable to form beige adipocytes. Despite successful knockdown, brown fat was completely unaffected by p300 deletion. As such, knockout mice showed a comparable metabolic profile to littermate controls in response to diet-induced obesity. Furthermore,de novobeige adipogenesis within subcutaneous fat by a β3adrenergic agonist remained intact in knockout mice. Although p300 and CBP have non-overlapping roles in other tissues, our results indicate p300 HAT activity is dispensable within thermogenic fats, likely due to functional compensation by CBP.