A regulatory element affects the activity and chromatin structure of the chicken α-globin 3′ enhancer

Gene promoters are frequently insufficient to drive the spatiotemporal patterns of gene expression during cell differentiation and organism development. Enhancers convey these properties through diverse mechanisms, including long-distance interactions with target promoters via their association with specific transcription factors. Despite unprecedented progress in the knowledge of enhancer mechanisms of action, there are still many unanswered questions. In particular, the contribution of an enhancer's local chromatin configuration to its mechanism of action is not completely understood. Here we describe a novel regulatory element, the Upstream Enhancer Element (UEE), which modulates the activity of the chicken α-globin 3′ enhancer by regulating its chromatin structure, specifically by positioning a nucleosome upstream of the core enhancer. This element binds nuclear factors and confers a more restricted activation on the α-globin 3′ enhancer, suggesting a progressive/rheostatic model for enhancer activity. Our results suggest that the UEE activity contributes to the positioning of a nucleosome that is necessary for the α-globin 3′ enhancer activation.