According to current models, once the cell has reached terminal differentiation, 
the enhancer repertoire is completely established and maintained by 
cooperatively acting lineage-specific transcription factors (TFs). TFs activated 
by extracellular stimuli operate within this predetermined repertoire, landing 
close to where master regulators are constitutively bound. Here, we describe 
latent enhancers, defined as regions of the genome that in terminally 
differentiated cells are unbound by TFs and lack the histone marks 
characteristic of enhancers but acquire these features in response to 
stimulation. Macrophage stimulation caused sequential binding of 
stimulus-activated and lineage-determining TFs to these regions, enabling 
deposition of enhancer marks. Once unveiled, many of these enhancers did not 
return to a latent state when stimulation ceased; instead, they persisted and 
mediated a faster and stronger response upon restimulation. We suggest that 
stimulus-specific expansion of the cis-regulatory repertoire provides an 
epigenomic memory of the exposure to environmental agents.