STUDIES ON SILENCING

沉默研究

• 批准号: 6422807
• 负责人: AMAR J KLAR
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/6422807
• 关键词: Schizosaccharomyces pombe; cell cycle; chromosomes; developmental genetics; fungal antigens; gene expression; gene induction /repression; genomic imprinting; meiosis; molecular biology; molecular genetics

Research: The Developmental Genetics Section is mainly interested in the genetics and molecular biology of gene silencing and mating-type switching in Schizosaccharomyces pombe. In this yeast, the mating-type region consists of three loci called mat1, mat2, and mat3. The mat2 and mat3 loci are always silent and only act as donors of genetic information required for switching the transcriptionally active mat1 locus. Studies on Silencing We previously found that silencing mechanism involves a chromosomally heritable epigenetic alteration, presumably of chromatin associated with the mat region. In collaboration with Dr. Shiv Grewal (a previous postdoc in our group) at Cold Spring Harbor Laboratory, we have discovered that swi6p performs imprinting function for silencing donor loci. Inheritance of stable states of gene expression is essential for cellular differentiation. In fission yeast, an epigenetic imprint marking the mating-type (mat2/3) region contributes to inheritance of the silenced state, but the nature of the imprint is not known. We show that a chromodomain-containing swi6 protein is a dosage-critical component involved in imprinting the mat locus. Transient overexpression of swi6p alters the epigenetic imprint at the mat2/3 region and heritably converts the expressed state to the silenced state. The establishment and maintenance of the imprint are tightly coupled to the recruitment and the persistence of swi6 at the mat2/3 region during mitosis as well as meiosis. Remarkably, swi6p remains bound to the mat2/3 interval throughout the cell and itself seems to be a component of the imprint. Our analyses suggest that the unit of inheritance at the mat2/3 locus comprises the DNA plus the associated swi6 protein complex.

调研：发育遗传学部分主要研究粟酒裂殖酵母中基因沉默和交配型转换的遗传学和分子生物学。 在这种酵母中，交配型区域由三个位点组成，称为mat 1，mat 2和mat 3。 mat 2和mat 3基因座总是沉默的，只作为转换转录活性mat 1基因座所需的遗传信息的供体。沉默的研究我们以前发现，沉默机制涉及一个染色体遗传的表观遗传改变，推测与垫区域相关的染色质。 在与冷泉港实验室的Shiv Grewal博士（我们小组以前的博士后）合作中，我们发现swi 6p具有沉默供体基因座的印迹功能。 基因表达稳定状态的遗传对于细胞分化是必不可少的。 在分裂酵母中，标记交配型（mat 2/3）区域的表观遗传印记有助于沉默状态的遗传，但印记的性质尚不清楚。 我们发现，一个含有染色体结构域的swi 6蛋白是一个剂量关键的组成部分，参与印迹的垫轨迹。 swi 6p的瞬时过表达改变了mat 2/3区域的表观遗传印记，并遗传性地将表达状态转化为沉默状态。 印记的建立和维持与swi 6在有丝分裂和减数分裂期间在mat 2/3区域的募集和持续紧密耦合。 值得注意的是，swi 6p在整个细胞中仍然与mat 2/3间隔结合，本身似乎是印记的一个组成部分。 我们的分析表明，在mat 2/3位点的遗传单位包括DNA加上相关的swi 6蛋白复合物。