We have further interrogated potential epigenetic mechanisms underlying Utx’s regulation of brown fat function during diet-induced obesity (DIO), and found that this process involves an interaction between histone and DNA methylation in the promoters of key molecules regulating brown or myogenic lineage determination, leading to a myogenic remodeling and thermogenic dysfunction in BAT of UTXKO mice during the development of DIO. Here, KDM6A is linked to obesity due to melanocortin 4 receptor deficiency.