Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

• DOI: 10.7554/elife.41266
• Publication Date: 2019-06-21T08:00:16Z
• Authors: Jeehae Park; Javier Estrada; Gemma Johnson; Ben J Vincent; Chiara Ricci-Tam; Meghan DJ Bragdon; Yekaterina Shulgina; Anna Cha; Zeba Wunderlich; Jeremy Gunawardena; Angela H DePace
• Keywords: Cooperativity; Blastoderm; Drosophila embryogenesis

Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a pattern in Drosophila blastoderm embryo response transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans that influence shape position driven by HbP2, find prevailing model, based on pairwise cooperative binding Bcd HbP2 is not adequate. demonstrate other proteins, such as pioneer factors, Mediator histone modifiers pattern. Comparing our results theory reveals how higher-order cooperativity energy expenditure impact boundary location sharpness. Our emphasize bacterial view regulation, where interactions between regulatory proteins dominate, must be reexamined animals, multiple molecular mechanisms collaborate function.