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.

研究：发育遗传学部分主要对精神分裂症中基因沉默和交配型转换的遗传学和分子生物学感兴趣。 在这种酵母中，交配型区域由三个位点组成，称为MAT1，MAT2和MAT3。 MAT2和MAT3基因座始终保持沉默，仅充当切换转录活性MAT1基因座所需的遗传信息的供体。关于沉默的研究，我们先前发现沉默机制涉及染色体可遗传的表观遗传学改变，大概是与MAT区域相关的染色质。 与冷春港实验室的Shiv Grewal博士（我们小组的先前的博士后）合作，我们发现SWI6P在沉默的供体位点执行烙印功能。 稳定基因表达状态的遗传对于细胞分化至关重要。 在裂变酵母中，标志着交配型（MAT2/3）区域的表观遗传印记有助于遗传沉默状态，但烙印的性质尚不清楚。 我们表明，含有染色体群的SWI6蛋白是涉及印记MAT基因座的一种剂量临界成分。 SWI6P的瞬时过表达改变了MAT2/3区域的表观遗传烙印，并且可以遗传地将表达状态转化为沉默状态。 烙印的建立和维护与有丝分裂和减数分裂过程中MAT2/3地区的募集和SWI6的持久性紧密结合。 值得注意的是，SWI6P在整个细胞中保持与MAT2/3间隔的结合，并且本身似乎是烙印的组成部分。 我们的分析表明，MAT2/3基因座的遗传单位包括DNA以及相关的SWI6蛋白复合物。