title: Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors.
abstract: The relatively simple combinatorial rules responsible for establishing the initial metameric expression of sloppy-paired-1 (slp1) in the Drosophila blastoderm embryo make this system an attractive model for investigating the mechanism of regulation by pair-rule transcription factors. This investigation of slp1 cis-regulatory architecture identifies two distinct elements, a proximal early stripe element (PESE) and a distal early stripe element (DESE) located from -3.1kb to -2.5kb and from -8.1kb to -7.1kb upstream of the slp1 promoter, respectively, that mediate this early regulation. The proximal element expresses only even-numbered stripes and mediates repression by Even-skipped (Eve) as well as by the combination of Runt and Fushi-tarazu (Ftz). A 272 basepair sub-element of PESE retains an Eve-dependent repression, but is expressed throughout the even-numbered parasegments due to the loss of repression by Runt and Ftz. In contrast, the distal element expresses both odd and even-numbered stripes and also drives inappropriate expression in the anterior half of the odd-numbered parasegments due to an inability to respond to repression by Eve. Importantly, a composite reporter gene containing both early stripe elements recapitulates pair-rule gene-dependent regulation in a manner beyond what is expected from combining their individual patterns. These results indicate that interactions involving distinct cis-elements contribute to the proper integration of pair-rule regulatory information. A model fully accounting for these results proposes that metameric slp1 expression is achieved through the Runt-dependent regulation of interactions between these two pair-rule response elements and the slp1 promoter.
authors.affiliation: Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794-5215, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Prazak
authors.forename: Miki
authors.initials: M
authors.lastname: Fujioka
authors.forename: J Peter
authors.initials: JP
authors.lastname: Gergen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001756:Blastoderm / Q000378:metabolism / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D014157:Transcription Factors