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首页> 外文学位 >Relationships between chromosome structure and long distance regulation of gene expression: A study of cis and trans modifiers of terminal deficiency-associated position effect variegation in a Drosophila melanogastor minichromosome.
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Relationships between chromosome structure and long distance regulation of gene expression: A study of cis and trans modifiers of terminal deficiency-associated position effect variegation in a Drosophila melanogastor minichromosome.

机译：染色体结构与基因表达的长距离调节之间的关系：果蝇黑腹果蝇微染色体末端缺陷相关位置效应变异的顺式和反式修饰子的研究。

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摘要

Genetic and cytological evidence indicate that chromosome structure and the organization of chromosomes within the interphase nucleus play major roles in the long-distance regulation of gene expression, and in chromosome inheritance. I have used the position effect variegation (PEV) associated with derivatives of Drosophila minichromosome Dp1187 to study cis and trans effects of chromosome structure and organization on gene expression. PEV is the clonal inactivation of a euchromatic gene that is located within or near heterochromatin. Terminal deletions of Dp1187 increase the PEV of the yellow+ gene located on it; this terminal deficiency-associated PEV (TDA-PEV) is suppressed by the presence of a second minichromosome, a novel phenomenon termed "trans -suppression". I examined the chromosomal elements responsible for trans-suppression using a series of minichromosomes with molecularly-characterized deletions and inversions. Full trans-suppression requires substantial chromosome homology, suggesting that chromosome pairing plays a key role in trans-suppression. These data indicate TDA-PEV and trans-suppression may reflect changes in nuclear positioning of the chromosomes and the gene, and/or distribution and activity of telomere binding proteins. My preliminary studies using fluorescence in situ hybridization (FISH) indicate the TDA-PEV and trans -suppressing minichromosomes pair in interphase nuclei, supplying corroborative evidence that trans-suppression involves chromosome pairing.; The proteins and mechanisms responsible for nuclear positioning, somatic pairing, and protecting and packaging chromosome ends in Drosophila have not been elucidated. To identify such proteins involved in these basic chromosomal functions, and to test models for long-distance regulation of gene expression, I screened for mutations that affect TDA-PEV and trans-suppression. Seventy-one mutations were identified. By mapping of these mutations, and characterizing them for their ability to affect other variegating alleles, I identified ten which specifically affect TDA-PEV. The remaining 61 mutations affect multiple types of PEV, suggesting they encode proteins with general roles in chromosome biology. Indeed, a high proportion of these mutations have a dominant effect on the transmission of a "centromere challenged" minichromosome, suggesting they affect genes critical in chromosome inheritance. My data indicate heterochromatin is a crucial component of normal chromosome function, and of the mechanisms undertaken by chromosome structure and nuclear organization in regulating gene expression and chromosome inheritance.
机译：遗传和细胞学证据表明，相间核内的染色体结构和染色体组织在基因表达的长距离调节和染色体遗传中起主要作用。我已经使用了与果蝇微染色体Dp1187衍生物相关的位置效应杂色（PEV），研究了染色体结构和组织对基因表达的顺式和反式作用。 PEV是位于异染色质之内或附近的常染色体基因的克隆失活。 Dp1187的末端缺失会增加位于其上的yellow +基因的PEV；这种终末缺陷相关的PEV（TDA-PEV）被第二个微染色体的存在所抑制，这是一种称为“反式抑制”的新现象。我使用一系列具有分子特征化的缺失和倒置的微型染色体检查了负责反式抑制的染色体元件。完全反式抑制需要实质的染色体同源性，这表明染色体配对在反式抑制中起关键作用。这些数据表明，TDA-PEV和反式抑制可能反映了染色体和基因的核位置变化和/或端粒结合蛋白的分布和活性。我使用荧光原位杂交（FISH）进行的初步研究表明，相间核中的TDA-PEV和反式抑制微型染色体对，提供了反式抑制涉及染色体配对的确证。还没有阐明负责果蝇中核定位，体细胞配对以及保护和包装染色体末端的蛋白质和机制。为了鉴定与这些基本染色体功能有关的蛋白质，并测试基因表达的远距离调节模型，我筛选了影响TDA-PEV和反式抑制的突变。鉴定出71个突变。通过绘制这些突变的图谱，并对它们影响其他杂色等位基因的能力进行表征，我确定了十个特异性影响TDA-PEV的基因。其余的61个突变影响多种类型的PEV，表明它们编码在染色体生物学中具有一般作用的蛋白质。确实，这些突变中的很大一部分对“着丝粒挑战”的微型染色体的传递起主要作用，这表明它们影响了染色体遗传中至关重要的基因。我的数据表明异染色质是正常染色体功能的重要组成部分，也是染色体结构和核组织在调节基因表达和染色体遗传中所起的机制的重要组成部分。

著录项

  • 作者

    Donaldson, Kathryn Marie.;

  • 作者单位

    University of California, San Diego.;

  • 授予单位 University of California, San Diego.;
  • 学科 Biology Genetics.
  • 学位 Ph.D.
  • 年度 2000
  • 页码 272 p.
  • 总页数 272
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遗传学;
  • 关键词

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