Substantial evidence supports the hypothesis that enhancers are critical 
regulators of cell-type determination, orchestrating both positive and negative 
transcriptional programs; however, the basic mechanisms by which enhancers 
orchestrate interactions with cognate promoters during activation and repression 
events remain incompletely understood. Here we report the required actions of 
LIM domain-binding protein 1 (LDB1)/cofactor of LIM homeodomain protein 
2/nuclear LIM interactor, interacting with the enhancer-binding protein 
achaete-scute complex homolog 1, to mediate looping to target gene promoters and 
target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter 
looping appears to be required for both activation and repression of these 
target genes. Although LDB1-dependent activated genes are regulated at the level 
of transcriptional initiation, the LDB1-dependent repressed transcription units 
appear to be regulated primarily at the level of promoter pausing, with LDB1 
regulating recruitment of metastasis-associated 1 family, member 2, a component 
of the nucleosome remodeling deacetylase complex, on these negative enhancers, 
required for the repressive enhancer function. These results indicate that 
LDB1-dependent looping events can deliver repressive cargo to cognate promoters 
to mediate promoter pausing events in a pituitary cell type.