A genomic analysis of doublesex function in sex determination

性别决定中双性功能的基因组分析

• 批准号: 8655457
• 负责人: Erin Alisa Jimenez
• 金额: $ 4.27万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8655457
• 关键词: Abdomen; Accounting; Adult; Affect; Animals; Belief; Cells; Characteristics; Chromosome Deletion; Comb animal structure; DNA Binding Domain; Defect; Dependency; Deposition; Development; Drosophila genus; Egg Yolk Proteins; Family; Fat Body; Female; Gene Expression; Gene Expression Profiling; Genes; Genomics; Gonadal structure; Hormonal; Human; Infertility; Link; Maintenance; Modeling; Mutation; Oocytes; Pathway interactions; Phenotype; Pheromone; Pigmentation physiologic function; Play; Proteins; RNA Splicing; Regulation; Research; Role; Sex Factors; Sterility; Structure; Syndrome; Tissues; Transcript; desaturase; external genitalia; fly; gain of function; interest; male; member; mutant; programs; public health relevance; research study; sex; sex determination; sexual dimorphism; trait; transcription factor; transcriptome sequencing

DESCRIPTION (provided by applicant): The sex determination mechanisms responsible for creating sexual dimorphism are diverse throughout the animal kingdom, such as cell autonomous splicing of specific sex factors in flies and hormonal secretion by gonads in humans, but converge upon a family of conserved genes, Dmrt's (dsx, mab-3 related transcription factors), that encode products that regulate sex specific gene expression. The Dmrt family of transcription factors share a common DNA-binding domain (DM domain), are expressed tissue specifically, and instruct those cells of the tissue they are expressed in to follow along a female or male developmental program. Moreover, chromosomal deletions affecting Dmrt's has been linked to a human syndrome of sex reversal. While the mechanisms by which sexual identity leads to sex-specific control of development are still being elucidated, the role of Dmrt's is most understood in Drosophila. The founding member of the Dmrt family, doublesex (dsx), was identified as a mutation affecting sexual differentiation resulting in an intersexual phenotype between males and females in Drosophila. In Drosophila, nearly all manifestations of sexual dimorphism are regulated by the presence of sex-specific transcripts, doublesex (dsx) and fruitless (fru), generated at the end of the sex determination cascade. Though this pathway has been established for many years, few direct targets for the DSX transcription factors are known. Direct targets of DSX include the yolk protein genes expressed in female fat body which encode yolk protein that get deposited in the oocytes; the bric-a-brac locus (bab1 and bab2) which encode transcription factors that regulate the presence sex-specific abdominal pigmentation; and desaturase-F which encodes a protein involved in female specific pheromone synthesis. Since interaction between DSX and its three known targets cannot account for the differences in regulation by DSX in all sexually dimorphic tissues it is expressed in, it is of great importance to identify direct and transcriptionally regulated targets f DSX.

描述（由申请人提供）：在整个动物界中，负责产生两性异形的性别决定机制是多种多样的，例如果蝇中特定性因子的细胞自主剪接和人类性腺的激素分泌，但集中于保守基因家族，Dmrt's（dsx，mAb-3相关转录因子），其编码调节性别特异性基因表达的产物。转录因子Dmrt家族共有一个共同的DNA结合结构域（DM结构域），组织特异性表达，并指导它们表达的组织的那些细胞遵循沿着雌性或雄性发育程序。此外，影响Dmrt的染色体缺失与人类性逆转综合征有关。 虽然性别认同导致发育的性别特异性控制的机制仍在阐明中，但Dmrt的作用在果蝇中最为人所知。Dmrt家族的创始成员doubletex（dsx）被鉴定为影响性分化的突变，导致果蝇中雄性和雌性之间的间性表型。在果蝇中，几乎所有的性二态性表现都受到性别特异性转录物的调节，doublemex（dsx）和fruitless（fru），它们产生于性别决定级联反应的末端。 尽管该途径已经建立多年，但已知DSX转录因子的直接靶点很少。DSX的直接靶标包括在雌性脂肪体中表达的卵黄蛋白基因，其编码沉积在卵母细胞中的卵黄蛋白; bric-a-brac基因座（bab 1和bab 2），其编码调节性别特异性腹部色素沉着的存在的转录因子;以及去饱和酶-F，其编码参与雌性特异性信息素合成的蛋白质。由于DSX和它的三个已知靶之间的相互作用不能解释DSX在其表达的所有性二型组织中的调节差异，因此鉴定DSX的直接和转录调节靶是非常重要的。