Proceedings of the National Academy of Sciences of the United States of America 105(22) , 7762-7767 (Jun 3 2008)
RNA Polymerase II (Pol II) is bound to the promoter regions of many or most developmental control genes before their activation during Drosophila embryogenesis. It has been suggested that Pol 11 stalling is used to produce dynamic and rapid responses of developmental patterning genes to transient cues such as extracellular signaling molecules. Here, we present a combined computational and experimental analysis of stalled promoters to determine how they come to bind Pol 11 in the early Drosophila embryo. At least one-fourth of the stalled promoters contain a shared sequence motif, the “pause button” (PB): KCGRWCG. The PB motif is sometimes located in the position of the DPE, and over one-fifth of the stalled promoters contain the following arrangement of core elements: GAGA, Inr, PB, and/or DPE. This arrangement was used to identify additional stalled promoters in the Drosophila genome, and permanganate footprint assays were used to confirm that the segmentation gene engrailed contains paused Pol 11 as seen for heat-shock genes. We discuss different models for Pol 11 binding and gene activation in the early embryo.