Enhancer activation is a critical step for gene activation. Here we report an 
epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 
methyltransferase) complex and the histone acetyltransferase p300. We 
demonstrate that UTX, in a demethylase activity-independent manner, facilitates 
conversion of inactive enhancers in embryonic stem cells to an active 
(H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of 
MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized 
by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The 
UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent 
stimulation of p300 recruitment, while MLL4-mediated H3K4 monomethylation, 
reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 
further enhances p300-dependent transcription. This work reveals a previously 
unrecognized cooperativity among enhancer-associated chromatin modulators, 
including a unique function for UTX, in establishing an "active enhancer 
landscape" and defines a detailed mechanism for the joint deposition of H3K4me1 
and H3K27ac.