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Characterization of the complete rat elastin gene: Analysis ofcis-acting elements involved in regulation of gene expression and alternative splicing and the role of repetitive sequences in gene instability.

机译:完整的大鼠弹性蛋白基因的表征:参与基因表达调控和选择性剪接的顺式作用元件分析,以及重复序列在基因不稳定中的作用。

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摘要

Elastin is the major component of elastic fibers which imparts the properties of extensibility and elastic recoil to tissues such as the nuchal ligament, aorta, lung and skin. The synthesis of this protein is subject to developmental and tissue-specific regulation. In addition several isoforms of tropoelastin, the insoluble precursor of elastin, have been identified and are believed to be the result of alternative splicing which is also controlled both developmentally and in a tissue-specific manner. We have isolated and characterized the rat tropoelastin gene to analyze putative cis-acting elements that may be involved in regulation of tropoelastin gene expression and alternative splicing.;We have screened two rat genomic libraries and isolated several overlapping recombinants that contained the entire rat elastin gene. These clones were subjected to extensive restriction and sequencing analyses. About 1 kbp of the rat tropoelastin promoter and the whole of intron 1 (about 8 kbp) were sequenced. Besides basic promoter elements and several transcription factor binding sites, an enhancer core sequence in the promoter and 4 enhancer core motifs in intron 1 were identified. In addition, the sequences of the promoter and intron 1 were studied to identify possible CpG islands. The roles different elements may play in developmental and tissue specific regulation of tropoelastin gene expression are discussed.;Exon-flanking sequences were analyzed. Comparison between alternatively spliced exons and exons that were not alternatively spliced showed that weak polypyrimidine tracts and branch point sequences may be involved in alternative splicing of exons 14 and 33. Stem-loop structures that form between exons 13 and 15 and their 5;Several repeat sequences were identified, and particularly in the 3
机译:弹性蛋白是弹性纤维的主要成分,其赋予诸如颈韧带,主动脉,肺和皮肤的组织可延展性和弹性反冲特性。该蛋白质的合成受到发育和组织特异性调节。另外,已经鉴定出弹性蛋白的不溶前体原弹性蛋白的几种同工型,并且据信这是选择性剪接的结果,该剪接也受到发育和组织特异性方式的控制。我们已经分离并鉴定了大鼠原弹性蛋白基因,以分析可能参与原弹性蛋白基因表达调控和选择性剪接的顺式作用元件;;我们筛选了两个大鼠基因组文库,并分离了包含整个大鼠弹性蛋白基因的几个重叠重组子。这些克隆进行了广泛的限制和测序分析。约1kbp的大鼠原弹性蛋白启动子和整个内含子1(约8kbp)被测序。除了基本的启动子元件和几个转录因子结合位点,还鉴定了启动子中的增强子核心序列和内含子1中的4个增强子核心基序。另外,研究了启动子和内含子1的序列以鉴定可能的CpG岛。讨论了不同元素在原弹性蛋白基因表达的发育和组织特异性调控中可能发挥的作用。;分析了外显子侧翼序列。交替剪接的外显子与未剪接的外显子之间的比较表明,弱的嘧啶区和分支点序列可能参与外显子14和33的选择性剪接。外显子13和15与它们的5之间形成茎环结构;多次重复确定了序列,特别是在3

著录项

  • 作者

    Alatawi, Abdulrahman.;

  • 作者单位

    Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey.;

  • 授予单位 Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey.;
  • 学科 Biochemistry.;Molecular biology.;Genetics.
  • 学位 Ph.D.
  • 年度 1994
  • 页码 248 p.
  • 总页数 248
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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