Studies on Silencing

研究&lt；/ B>;<;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;；在这种酵母中，交配型区域由三个位点组成，分别是&lt；I>mat1</ I>, <I>mat2</ I&gt；和&lt；I>mat3</ I&gt；。这些&lt；I>mat2</ I&gt；和&lt；I>mat3</ I&gt；位点总是沉默的，它们只作为开关转录活性&lt；I>mat1</ I&gt；位点&lt；BR><BR>< BR><BR>&lt；的遗传信息的供体。沉默&lt；/ B> <BR>&lt；在裂变酵母中，标记交配型（<I>mat2/3</ I>）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。我们发现含有swi6蛋白的染色体结构域是一个剂量关键成分，参与印迹&lt；I>mat</ I&gt；位点。印迹的建立和维持与有丝分裂和减数分裂期间swi6在&lt；I>mat2/3</ I&gt；区域的募集和持续紧密相关。值得注意的是，swi6p在整个细胞中仍然与&lt；I>mat2/3</ I&gt；间隔相结合，并且它本身似乎是印记的一个组成部分。我们的分析表明，在&lt；I>mat2/3</ I&gt；位点上的遗传单位包括DNA和相关的swi6蛋白复合物。有趣的是，沉默区域被1.2KB的反向重复序列所包围，该序列阻断了异染色质向相邻染色体区域的扩散。我们已经发现，脱氧核糖核苷酸生物合成中的突变导致沉默在这些异染色质屏障上的传播。异染色质跨越屏障的扩散需要功能性Atf1/Pcr1， ATF-CREB家族蛋白，但不需要rna干扰Dcr1， Ago1或Rdp1因子，这些因子先前与沉默有关。我们对意志的研究继续确定沉默的遗传决定因素。这项工作对解释真核细胞分化和癌症发展具有直接意义，因为表观遗传控制的破坏构成了不需要的细胞生长的重要机制。

<B>Research</b>:<BR><BR>The Developmental Genetics Section is mainly interested in the genetics and molecular biology of gene silencing and mating-type switching in <I>Schizosaccharomyces pombe</i>. In this yeast, the mating-type region consists of three loci called <I>mat1</i>, <I>mat2</i>, and <I>mat3</i>. The <I>mat2</i> and <I>mat3</i> loci are always silent and only act as donors of genetic information required for switching the transcriptionally active <I>mat1</i> locus.<BR><BR><B>Studies on Silencing</b><BR><BR>We previously found that silencing mechanism involves a chromosomally heritable epigenetic alteration, presumably of chromatin associated with the <I>mat</i> region. In fission yeast, an epigenetic imprint marking the mating-type (<I>mat2/3</i>) 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 <I>mat</i> locus. The establishment and maintenance of the imprint are tightly coupled to the recruitment and the persistence of swi6 at the <I>mat2/3</i> region during mitosis as well as meiosis. Remarkably, swi6p remains bound to the <I>mat2/3</i> interval throughout the cell and itself seems to be a component of the imprint. Our analyses suggest that the unit of inheritance at the <I>mat2/3</i> locus comprises the DNA plus the associated swi6 protein complex. Interestingly the silenced domain is bracketed by 1.2KB inverted repeat sequences that block spreading of heterochromatin to adjoining regions of chromosome. We have discovered that mutations in deoxyribonucleotide biosynthesis cause spreading of silencing across these heterochromatin barriers. The spreading of heterochromatin across barriers required functional Atf1/Pcr1, ATF-CREB family proteins, but not the RNA-interference Dcr1, Ago1, or Rdp1 factors, previously implicated in silencing. Our work on will continues to define the genetic determinants of silencing. This work has direct implication for explaining eucaryotic cellular differentiation and for cancer development as disruption of epigenetic controls constitutes a prominant mechanism of unwanted cellular growth.