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: 8529878
• 负责人: Erin Alisa Jimenez
• 金额: $ 4.22万
• 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/8529878
• 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）：负责产生性二态性的性别决定机制在整个动物界是多种多样的，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。 Dmrt 转录因子家族共享一个共同的 DNA 结合域（DM 域），在组织中特异性表达，并指导其表达所在组织的细胞遵循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症有关。 虽然性别认同导致性别特异性发育控制的机制仍在阐明中，但 Dmrt 的作用在果蝇中最为人们所了解。 Dmrt 家族的创始成员 doublesex (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出现间性表型。在果蝇中，几乎所有性二态性的表现都受到性别特异性转录本（双性（dsx）和无果（fru）的存在的调节，这些转录本是在性别决定级联结束时产生的）。 尽管该通路已建立多年，但 DSX 转录因子的直接靶标却鲜为人知。 DSX 的直接目标包括女性脂肪体中表达的卵黄蛋白基因，这些基因编码沉积在卵母细胞中的卵黄蛋白； bric-a-brac 基因座（bab1 和 bab2），编码调节性别特异性腹部色素沉着的转录因子；去饱和酶-F编码参与雌性特异性信息素合成的蛋白质。由于 DSX 与其三个已知靶标之间的相互作用无法解释 DSX 在其表达的所有性二态性组织中的调节差异，因此鉴定 DSX 的直接转录调节靶标非常重要。