title: Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins.
abstract: Somatic sex determination in Drosophila depends on the expression of Sex-lethal (Sxl), whose level is determined by the relative number of X chromosomes and sets of autosomes (X:A ratio). The first step in regulation of Sxl expression is transcriptional control from its early promoter and several genes encoding transcription factors of the helix-loop-helix (HLH) family such as daughterless (da), sisterless-b (sis-b), deadpan (dpn) and extramacrochaetae (emc) have been implicated. By the use of transfection assays and in vitro binding experiments, here we show that da/sis-b heterodimers bind several sites on the Sxl early promoter with different affinities and consequently tune the level of active transcription from this promoter. Interestingly, our data indicate that repression by the dpn product of da/sis-b dependent activation results from specific binding of dpn protein to a unique site within the promoter. This contrasts with the mode of emc repression, which inhibits the formation of the da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sxl gene transcription is positively or negatively regulated to control somatic sex determination.
authors.affiliation: Department of Biophysics, Faculty of Science, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hoshijima
authors.forename: A
authors.initials: A
authors.lastname: Kohyama
authors.forename: I
authors.initials: I
authors.lastname: Watakabe
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shimura
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D007301:Insect Hormones / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000737:chemistry*; D012732:Sex Determination Analysis; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C090080:Da protein, Drosophila; C067777:Sxl protein, Drosophila; C089197:sc protein, Drosophila; C078020:Dpn protein, Drosophila