We used genome-wide sequencing methods to study stimulus-dependent enhancer 
function in mouse cortical neurons. We identified approximately 12,000 neuronal 
activity-regulated enhancers that are bound by the general transcriptional 
co-activator CBP in an activity-dependent manner. A function of CBP at enhancers 
may be to recruit RNA polymerase II (RNAPII), as we also observed 
activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at 
enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) 
within enhancer domains defined by the presence of histone H3 monomethylated at 
lysine 4. The level of eRNA expression at neuronal enhancers positively 
correlates with the level of messenger RNA synthesis at nearby genes, suggesting 
that eRNA synthesis occurs specifically at enhancers that are actively engaged 
in promoting mRNA synthesis. These findings reveal that a widespread mechanism 
of enhancer activation involves RNAPII binding and eRNA synthesis.