Regulation Of Cellular Proliferation And Diversity In Dr

博士中细胞增殖和多样性的调节

• 批准号: 6534886
• 负责人: JAMES A. KENNISON
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6534886
• 关键词: Drosophilidae; arthropod genetics; cell differentiation; cell growth regulation; cell proliferation; chromosome aberrations; developmental genetics; gene induction /repression; gene interaction; genetic models; genetic transcription; homeobox genes; molecular cloning; nucleic acid sequence; transcription factor

Genes involved in the determination and differentiation of segmental identity in Drosophila melanogaster have been identified by genetic interactions with the homeotic genes already known to be required. Many new genes required for transcriptional activation or repression of the homeotic genes have been identified. We have cloned and characterized one of the genes required for transcriptional repression. The new homeotic transcriptional repressor, Su(z)12, encodes a zinc-finger protein conserved between Drosophila, plants, and vertebrates. It is required both during embryogenesis and later in development to maintain repression of homeotic genes. We have also localized the verthandi transcriptional activator to the middle of the centric heterochromatin of one of the autosomes. We have also continued our genetic and developmental characterization of the brahma chromatin remodeling complex, which is also required for transcriptional activation of homeotic genes in Drosophila. We have identified cis-regulatory elements in two target genes and have been isolating mutations that specifically disrupt interactions of brahma with these two different target genes. We have also identified transcriptional regulatory elements in the Sex combs reduced homeotic gene that are involved in both cis-regulation and in regulatory interactions between genes on homologous chromosomes. The regulatory interactions between genes on homologous chromosomes result from transvection. The dominant effects of chromosome aberrations in this genomic region suggest that interactions between multiple silencing elements are important for the maintenance of transcriptional repression during development.

通过与已经已知所需的同源基因的遗传相互作用，已经鉴定出参与果蝇中分段身份确定和分化的基因。已经确定了转录激活或抑制同源基因所需的许多新基因。我们已经克隆并表征了转录抑制所需的基因之一。新的同源转录阻遏物SU（Z）12编码果蝇，植物和脊椎动物之间保守的锌指蛋白。在胚胎发生期间和后来的发育过程中，都需要维持对同源基因的抑制。我们还将verthandi转录激活剂定位在一个常染色体的中心异染色质中间。我们还继续对梵天染色质重塑复合物的遗传和发育表征，这也是果蝇中同源基因的转录激活所必需的。我们已经确定了两个靶基因中的顺式调节元件，并一直在分离突变，这些突变特异性破坏了梵天与这两个不同的靶基因的相互作用。我们还确定了性梳中的转录调节元件减少了同源染色体上基因的基因相互作用的同源基因。基因对同源染色体的基因之间的调节相互作用是由于转向反转而导致的。在该基因组区域中染色体畸变的主要作用表明，多个沉默元件之间的相互作用对于维持发育过程中转录抑制很重要。