title: Computational models for neurogenic gene expression in the Drosophila embryo.
abstract: The early Drosophila embryo is emerging as a premiere model system for the computational analysis of gene regulation in development because most of the genes, and many of the associated regulatory DNAs, that control segmentation and gastrulation are known. The comprehensive elucidation of Drosophila gene networks provides an unprecedented opportunity to apply quantitative models to metazoan enhancers that govern complex patterns of gene expression during development. Models based on the fractional occupancy of defined DNA binding sites have been used to describe the regulation of the lac operon in E. coli and the lysis/lysogeny switch of phage lambda. Here, we apply similar models to enhancers regulated by the Dorsal gradient in the ventral neurogenic ectoderm (vNE) of the early Drosophila embryo. Quantitative models based on the fractional occupancy of Dorsal, Twist, and Snail binding sites raise the possibility that cooperative interactions among these regulatory proteins mediate subtle differences in the vNE expression patterns. Variations in cooperativity may be attributed to differences in the detailed linkage of Dorsal, Twist, and Snail binding sites in vNE enhancers. We propose that binding site occupancy is the key rate-limiting step for establishing localized patterns of gene expression in the early Drosophila embryo.
authors.affiliation: Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720-3204, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Zinzen
authors.forename: Kate
authors.initials: K
authors.lastname: Senger
authors.forename: Mike
authors.initials: M
authors.lastname: Levine
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papatsenko
mesh_terms: D000818:Animals; D001483:Base Sequence; D003198:Computer Simulation; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D020880:Neuregulins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C081481:Rho protein, Drosophila; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C062236:dl protein, Drosophila; C000604451:sna protein, Drosophila; C094797:vnd protein, Drosophila; C102104:vn protein, Drosophila