title: Different modes of enhancer-specific regulation by Runt and Even-skipped duringDrosophilasegmentation.
abstract: The initial metameric expression of theDrosophila sloppy paired 1(slp1) gene is controlled by two distinctcis-regulatory DNA elements that interact in a nonadditive manner to integrate inputs from transcription factors encoded by the pair-rule segmentation genes. We performed chromatin immunoprecipitation on reporter genes containing these elements in different embryonic genotypes to investigate the mechanism of their regulation. The distal early stripe element (DESE) mediates both activation and repression by Runt. We find that the differential response of DESE to Runt is due to an inhibitory effect of Fushi tarazu (Ftz) on P-TEFb recruitment and the regulation of RNA polymerase II (Pol II) pausing. The proximal early stripe element (PESE) is also repressed by Runt, but in this case, Runt prevents PESE-dependent Pol II recruitment and preinitiation complex (PIC) assembly. PESE is also repressed by Even-skipped (Eve), but, of interest, this repression involves regulation of P-TEFb recruitment and promoter-proximal Pol II pausing. These results demonstrate that the mode ofslp1repression by Runt is enhancer specific, whereas the mode of repression of theslp1PESE enhancer is transcription factor specific. We propose a model based on these differential regulatory interactions that accounts for the nonadditive interactions between the PESE and DESE enhancers duringDrosophilasegmentation.
authors.affiliation: Department of Biochemistry and Cell Biology and Center for Developmental Genetics and.|Graduate Program in Biochemistry and Structural Biology, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Saiyu
authors.initials: S
authors.lastname: Hang
authors.affiliation: Department of Biochemistry and Cell Biology and Center for Developmental Genetics and john.peter.gergen@stonybrook.edu.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Gergen
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005260:Female; D051717:Fushi Tarazu Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C052837:eve protein, Drosophila; C497169:ftz protein, Drosophila; C080833:run protein, Drosophila; C074838:slp1 protein, Drosophila