Studies on mat1 imprinting

mat1印迹研究

基本信息

  • 批准号:
    8763091
  • 负责人:
  • 金额:
    $ 53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

The pattern of switching of Schizosaccharomyces pombe (S. pombe)cells is nonrandom when assayed by single cell pedigrees. After two consecutive asymmetric cell divisions, one in four "granddaughter" cells undergoes a mating-type switch. Previously, we showed that this pattern is due to mat1 imprinting that marks only one sister chromatid in a strand-specific manner, and is related to a site-specific, double-stranded DNA break at mat1. We now show that this imprint is a strand-specific, alkali-labile DNA modification at mat1. The DNA break is an artifact, created from the imprint during DNA purification. We also proposed and tested the model that mat1 is preferentially replicated by a centromere-distal origin(s), so that the strand-specific imprint occurs only during lagging-strand synthesis. Altering the origin of replication, inverting mat1, or introducing an origin of replication affects the imprinting and switching efficiencies in predicted ways. Two-dimensional gel analysis confirmed that mat1 is preferentially replicated by a centromere-distal origin(s). Thus, the DNA replication machinery may confer different developmental potential to sister cells. Our recent work has discovered the biochemical functions of the swi1 and swi3 genes. We found that swi1p and swi3p perform imprinting by pausing and terminating DNA replication at mat1. Our work shows that: 1) the factors swi1p and swi3p act by pausing the replication fork at the imprinting site, and 2) swi1p and swi3p are involved in termination at the mat1-proximal polar-terminator of replication (RTS1). We performed a genetic screen to identify these termination factors and identified an allele that separated the pausing/imprinting and termination functions of swi1p. Our results suggest that swi1p and swi3p promote imprinting in novel ways, both by pausing replication at mat1 and by terminating replication at RTS1. We also showed that Swi1 and Swi3 proteins form a complex in vivo and that both proteins bind to the RTS1 and the mat1 replication pause sites on the chromosome. Future studies will be designed to define the mechanism of imprinting. We have already identified a large number of mat1 mutations that affect imprinting. Molecular analysis of these mat1 mutations should help us define the mechanism of imprinting.
当单细胞谱系分析时,pombe Schizosaccharomyces pombe (S. pombe)细胞的开关模式是非随机的。在连续两次不对称细胞分裂后,四分之一的“孙女”细胞经历了交配型转换。先前,我们发现这种模式是由于mat1印迹仅以链特异性的方式标记一个姐妹染色单体,并且与mat1位点特异性的双链DNA断裂有关。我们现在表明,这个印记是一个链特异性的,碱不稳定的DNA修饰在mat1。DNA断裂是一种人工制品,是在DNA纯化过程中由印记产生的。我们还提出并测试了mat1优先由着丝粒远端起源复制的模型,因此链特异性印记仅在滞后链合成期间发生。改变复制起始点、反转mat1或引入复制起始点会以可预测的方式影响印迹和转换效率。二维凝胶分析证实,mat1优先由着丝粒远端起源复制。因此,DNA复制机制可能赋予姊妹细胞不同的发育潜能。我们最近的工作已经发现了swi1和swi3基因的生化功能。我们发现swi1p和swi3p通过暂停和终止mat1上的DNA复制来执行印迹。我们的研究表明:1)swi1p和swi3p因子通过在印迹位点暂停复制叉起作用,2)swi1p和swi3p参与了复制的mat1-近端极性终止(RTS1)的终止。我们进行了遗传筛选来鉴定这些终止因子,并鉴定了一个分离swi1p暂停/印记和终止功能的等位基因。我们的研究结果表明,swi1p和swi3p通过暂停mat1位点的复制和终止RTS1位点的复制,以新颖的方式促进印迹。我们还发现Swi1和Swi3蛋白在体内形成复合体,并且这两种蛋白都与染色体上的RTS1和mat1复制暂停位点结合。未来的研究将旨在确定印迹的机制。我们已经发现了大量影响印迹的mat1突变。对这些mat1突变的分子分析将有助于我们确定印迹的机制。

项目成果

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AMAR J KLAR其他文献

AMAR J KLAR的其他文献

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{{ truncateString('AMAR J KLAR', 18)}}的其他基金

1999 GORDON RESEARCH CONFERENCE ON EPIGENETIC EFFECTS
1999 年戈登表观遗传效应研究会议
  • 批准号:
    6043619
  • 财政年份:
    1999
  • 资助金额:
    $ 53万
  • 项目类别:
COLD SPRING HARBOR ADVANCED BACTERIAL GENETICS COURSE
冷泉港高级细菌遗传学课程
  • 批准号:
    3434862
  • 财政年份:
    1980
  • 资助金额:
    $ 53万
  • 项目类别:
COLD SPRING HARBOR ADVANCED BACTERIAL GENETICS COURSE
冷泉港高级细菌遗传学课程
  • 批准号:
    3434863
  • 财政年份:
    1980
  • 资助金额:
    $ 53万
  • 项目类别:
MOLECULAR MECHANISMS OF DIFFERENTIATION
分化的分子机制
  • 批准号:
    3273231
  • 财政年份:
    1978
  • 资助金额:
    $ 53万
  • 项目类别:
MOLECULAR MECHANISMS OF DIFFERENTIATION
分化的分子机制
  • 批准号:
    3273230
  • 财政年份:
    1978
  • 资助金额:
    $ 53万
  • 项目类别:
Studies on Silencing
沉默研究
  • 批准号:
    6559242
  • 财政年份:
  • 资助金额:
    $ 53万
  • 项目类别:
HUMAN HANDEDNESS STUDIES
人类惯用手研究
  • 批准号:
    6423737
  • 财政年份:
  • 资助金额:
    $ 53万
  • 项目类别:
STUDIES ON SILENCING
沉默研究
  • 批准号:
    6422807
  • 财政年份:
  • 资助金额:
    $ 53万
  • 项目类别:
Studies on mat1 Imprinting
mat1 印迹研究
  • 批准号:
    7338512
  • 财政年份:
  • 资助金额:
    $ 53万
  • 项目类别:
Studies on mat1 Imprinting
mat1 印迹研究
  • 批准号:
    7053122
  • 财政年份:
  • 资助金额:
    $ 53万
  • 项目类别:

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  • 批准号:
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    1998
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    Collaborative Research and Development Grants
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    200906-1996
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