Burtis KC, Coschigano KT, Baker BS, Wensink PC. The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. EMBO J 10: 2577-2582

Department of Genetics, University of California, Davis 95616.
The EMBO Journal (Impact Factor: 10.43). 10/1991; 10(9):2577-82.
Source: PubMed


The doublesex (dsx) gene of Drosophila melanogaster encodes both male-specific and female-specific polypeptides, whose synthesis is regulated by alternative sex-specific splicing of the primary dsx transcript. The alternative splicing of the dsx mRNA is the last known step in a cascade of regulatory gene interactions that involves both transcriptional and post-transcriptional mechanisms. Genetic studies have shown that the products of the dsx locus are required for correct somatic sexual differentiation of both sexes, and have suggested that each dsx product functions by repressing expression of terminal differentiation genes specific to the opposite sex. However, these studies have not shown whether the dsx gene products function directly to regulate the expression of target genes, or indirectly through another regulatory gene. We report here that the male- and female-specific DSX proteins, expressed in E.coli, bind directly and specifically in vitro to three DNA sequences located in an enhancer region that regulates female-specific expression of two target genes, the yolk protein genes 1 and 2. This result suggests strongly that dsx is a final regulatory gene in the hierarchy of regulatory genes controlling somatic sexual differentiation.

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    • "Although DSX has been studied for 50 years, there are still few defined DSX targets, and these cannot fully explain the sexually dimorphic morphologies and behaviors regulated by dsx. The known DSX target genes were identified on a case-by-case basis (Burtis et al., 1991; Shirangi et al., 2009; Williams et al., 2008). There have been large numbers of genome-wide expression studies on the sexes, but few attempts to link this expression directly to DSX (Lebo et al., 2009). "
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    ABSTRACT: Primary sex-determination ''switches'' evolve ra-pidly, but Doublesex (DSX)-related transcription fac-tors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female-and male-specific isoforms (DSX F and DSX M), but little is known about how dsx controls sexual development, whether DSX F and DSX M bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site predic-tion, and evolutionary conservation. We find that DSX F and DSX M bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex-and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway compo-nents providing for direct and indirect regulation of sex-biased expression. INTRODUCTION
    Full-text · Article · Dec 2014 · Developmental Cell
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    • "That DSXM and DSXF can be utilized differentially has been previously established. In the fat body, female-specific expression of Yp1 and Yp2 depends on up-regulation by DSXF in females and down-regulation by DSXM in males [8], [10], [74]. Thus, in dsx null flies, both sexes express these genes at equivalent levels. "
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    ABSTRACT: Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female characteristics across a variety of tissues. To explore how cellular and developmental contexts integrate with doublesex (dsx) gene function, we focused on the sexually dimorphic number of gustatory sense organs (GSOs) in the foreleg. We show that DSX(M) and DSX(F) promote and repress GSO formation, respectively, and that their relative contribution to this dimorphism varies along the proximodistal axis of the foreleg. Our results suggest that the DSX proteins impact specification of the gustatory sensory organ precursors (SOPs). DSX(F) then acts later in the foreleg to regulate gustatory receptor neuron axon guidance. These results suggest that the foreleg provides a unique opportunity for examining the context-dependent functions of DSX.
    Full-text · Article · Dec 2012 · PLoS ONE
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    • "The gene coding for Vitellogenin (Vg) has been characterized as a target for Dsx protein in D. melanogaster47. Previous studies have shown that the basal levels of vg gene expression is up regulated by the female form of Dsx protein (DsxF) and down regulated by the male form of Dsx protein (DsxM)16334748. In T. castaneum, two genes [vg1 (Glean-13602) and vg2 (Glean-10839)] coding for Vg have been identified and both the genes show identical patterns of expression49. Both vg1 and vg2 mRNA levels were quantified in Tcdsx knockdown and control insects. "
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    ABSTRACT: Sex determination cascade in insects terminates with the production of sex-specific protein, Doublesex (Dsx). We identified the dsx homolog (Tcdsx) in Tribolium castaneum. The pre-mRNA of Tcdsx is sex-specifically spliced into three female (Tcdsxf1, Tcdsxf2 and Tcdsxf3) and one male-specific (Tcdsxm) isoforms. Cis-regulatory elements potentially involved in sex-specific splicing of the Tcdsx pre-mRNA were identified in the female-specific exon and the adjoining intronic sequences. All the three female-specific TcDsx proteins share common OD1 and OD2 domains and differ in their C-terminal sequences. Knockdown of Tcdsx resulted in a reduction in the oocyte development, egg production and hatching of eggs laid. Several genes, including those coding for Vitellogenins and Vitellogenin receptors were identified as targets of TcDsx. RNAi experiments showed an isoform-specific targeting of identified target genes by TcDsx as knockdown in the expression of Tcdsx isoforms individually or in combinations resulted in differential effects on the expression of target genes.
    Full-text · Article · Dec 2012 · Scientific Reports
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