STUDIES ON SILENCING

研究：发育遗传学部分主要对裂殖酵母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，交配型区域由三个基因座组成，分别称为mat1、mat2和mat3。Mat2和mat3基因座总是沉默的，只作为基因信息的供体，需要切换转录活性的mat1基因座。沉默的研究我们以前发现沉默机制涉及染色体可遗传的表观遗传改变，推测是与MAT区域相关的染色质改变。在与冷泉港实验室的Shiv Grewal博士(我们团队的前博士后)的合作下，我们发现swing6p具有抑制供体基因座的印记功能。基因表达稳定状态的遗传对细胞分化至关重要。在分裂酵母中，标记交配型(mat2/3)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。我们表明，一个含铬结构域的sw6蛋白是印记MAT基因的剂量关键成分。Swi6p的瞬时过表达改变了mat2/3区域的表观遗传印记，并遗传地将表达状态转换为沉默状态。印迹的建立和维持与有丝分裂和减数分裂过程中Swi6在mat2/3区域的招募和持久性密切相关。值得注意的是，wi6p仍然与整个细胞的mat2/3区间结合，它本身似乎是印记的一个组成部分。我们的分析表明，mat2/3基因座的遗传单位由DNA加上相关的sw6蛋白复合体组成。

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.