NSF Award
0323957
An important question in molecular biology is how intricate biological processes such as embryonic development are achieved through the actions of regulatory molecules. In the fruit fly Drosophila, the early embryonic patterning along the anterior-posterior axis is instructed by the homeodomain-containing transcriptional activator Bicoid (Bcd), which initiates the cascade of the patterning programs by turning on specific target genes required for anterior development. Despite extensive studies of Bcd as an activator and molecular morphogen, it remains unclear how Bcd activates transcription of its target genes and what proteins participate in the activation process in embryos. This project is designed to test the hypothesis that Bcd activates transcription by facilitating the formation of the transcription machinery at target gene promoters during development. There are three specific aims in this project. Aim 1 will directly analyze, using a chromatin immunoprecipitation (ChIP) assay, the occupancy of general transcription factors at target gene promoters in wild type and bcd-deficient embryos. Aim 2 will further dissect the interaction between Bcd and TFIIB and determine the biological importance of this interaction during development. Aim 3 will study the role of histone acetylation and, in particular, the co-activator CBP in facilitating the action of Bcd in embryos. This project takes advantage of both biochemical and genetic techniques, focusing on the objective of revealing mechanistic insights relevant to early embryonic patterning in Drosophila.
