We propose that expression of MN effector genes is maintained by transient enhancers bound by Isl1/Lhx3 in nascent MNs and Isl1/Onecut1 in maturing hypaxial MNs. The median distance between the closest day 5 and day 6 Isl1-bound sites is 109 kb (Figure S2D), indicating engagement of a large genomic territory in the regulation of MN gene expression. Isl1 is preferentially recruited to enhancers containing clusters of stage-specific TFs. We propose that stage-specific Isl1 binding leads to the recruitment of the histone acetyl transferase p300, acetylation of H3K27, and transient activation of enhancers. Following Isl1 release, enhancers are rapidly deactivated and decommissioned as manifested by the loss of p300, H3K27ac, and chromatin accessibility.