Holocomplex model of LCR/promoter functional interactions illustrating a putative DNA looping event between 5′HS1 and the distal promoter element. In this model, 5′HS1 interacts with the distal promoter element and tethers the transcriptional enhancement activities of a 5′HS2-4 holocomplex to the proximal promoter element and recruits polymerase. The proposed architectural role of 5′HS1 and the distal promoter facilitates alignment of 5′HS2-4 with the proximal promoter. 3′ sequences are required either to establish and/or maintain open chromatin or directly influence promoter activity.