title: Autoregulatory feedback controls sequential action of cis-regulatory modules at the brinker locus.
abstract: cis-regulatory modules (CRMs) act sequentially to regulate temporal expression of genes, but how the switch from one to the next is accomplished is not well understood. To provide insight, here we investigate the cis-regulatory system controlling brinker (brk) expression in the Drosophila embryo. Two distally located CRMs support expression at different times, while a promoter-proximal element (PPE) is required to support their action. In the absence of Brk protein itself or upon mutagenesis of Brk binding sites within the PPE, the late-acting CRM, specifically, is delayed. This block to late-acting CRM function appears to be removed when the early-acting CRM is also deleted. These results demonstrate that autoregulatory feedback is necessary for the early-acting CRM to disengage from the promoter so that the late-acting CRM may act. Autoregulation may be a commonly used mechanism to control sequential CRM action necessary for dynamic gene expression throughout the course of development.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Dunipace
authors.forename: Abbie
authors.initials: A
authors.lastname: Saunders
authors.forename: Hilary L
authors.initials: HL
authors.lastname: Ashe
authors.forename: Angelike
authors.initials: A
authors.lastname: Stathopoulos
mesh_terms: D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D012097:Repressor Proteins; C118082:brk protein, Drosophila
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