An Epigenome Atlas of Mouse Adipocytes

Despite recent advances in the characterization of the mouse adipocyte epigenome, epigenetic characterization of adipocytes in vivo has been limited, particularly across different adipose depots and of more than two epigenetic modifications. In this study, by using the state-of-the art method CUT&Tag and NuTRAP mice to generate paired single mouse datasets we conducted an integrative multimodal analysis of five histone marks – H3K4me3, H3K27me3, H3K4me1, H3K27ac and H3K9me3 – in beige, brown, and white adipocytes from three distinct mouse adipose tissue depots. Our analysis revealed that enhancers distinguished adipocytes by their tissue of origin, with H3K4me1 deposition differentiating between beige and brown adipocytes. Furthermore, diphtheria toxin-mediated ablation of beige adipocytes showed that white adipocytes in inguinal adipose tissue and beige adipocytes did not use a distinct enhancer set and both poised thermogenic genes for expression. In contrast, adipocytes from epididymal adipose tissue actively repressed thermogenic master regulators and exhibited a distinct enhancer profile compared to white adipocytes from inguinal tissue. These paired multimodal data comprise an extensive resource for the further exploration of the mouse adipocyte epigenome which may enable discovery of regulatory elements governing adipocyte identity and gene regulation. Ucp1ERCre x NuTRAP mice were cold exposed at 8 degrees celsius for one week and received tamoxifen during this time. Subesquently mice were either sacrificed or allowed to recover for 8 weeks at 22 or 30 degrees celsius before tissue harvest. AdipoCre x NuTRAP mice were housed either at 22 or 30 degrees before tissue harvest. AdipoCre x NuTRAP x Ucp1DTRGfp mice were old exposed at 8 degrees celsius for one week and were injected with diphtheria toxin or saline thereafter before tissue harvest. Labelled adipocyte nuclei of brown, inguinal and epididymal adipose tissue were isolated and used for CUT&Tag. 2-3 biological replicates per hPTM and condition. Datasets are paired per mouse.