Jae Lee has purified two important transcriptional coactivator complexes, ASC-1 complex, which links splicing to transcription, and ASC-2 complex (ASCOM, aka MLL3/4-complexes), which represents the first histone H3 lysine 4 methyltransferase (H3K4MT) complex identified in mammals (containing either the H3K4MT MLL3/KMT2C or its paralog MLL4/KMT2D). ASCOM belongs to a family of similar mammalian complexes, collectively named Set1-like complexes. In humans, mutations in MLL4 but not MLL3 are known to cause a developmental disorder named Kabuki syndrome. In a striking demonstration of a specificity of individual Set1-like complexes, Lee discovered that mutant mouse models for Mll4 (but NOT Mll3) also recapitulate many features of the Kabuki syndrome. More recently, Lee has begun pioneering the gene regulatory network responsible for embryonic development of hypothalamic arcuate neurons that control feeding, energy expenditure, reproduction and growth.