Figure 7.

A model of KDM1A-mediated homeostasis of enhancers during their life cycle. TF binding and subsequent recruitment of methyltransferases, KMT2C/D, prime an enhancer with H3K4me1 and/or H3K4me2. KDM1A is then recruited to this enhancer by yet unknown H3K4me-sensing mechanisms and cooperates with histone deacetylases (HDACs) to suppress its aberrant activation. A primed enhancer, depending on further regulatory signals, can become either “active” or “poised.” The presence of KDM1A/HDACs is required to antagonize the activities of the methyltransferases and acetyltransferases (HATs) and maintain an optimal histone modification landscape. The equilibrium of these counteractions likely defines the activity of an enhancer. When an enhancer is decommissioned upon the loss of TF binding, KDM1A may remove the remnant H3K4me1/2 before dissociating and rendering it latent.