...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleus >Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells
【24h】

Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells

机译：富含基因的染色体区域优先位于非典型早衰细胞的层状B缺陷型核泡中

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

More than 20 mutations in the gene encoding A-type lamins (LMNA ) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to other transcription factors. Our results suggest that the p.S143F progeria mutation has a severe impact not only on the structure of the lamina but also on the organization of interphase chromatin domains and transcription. These structural defects are likely to contribute to gene expression changes reported in progeria and other types of laminopathies.
机译：编码A型核纤层蛋白（LMNA）的基因中有20多个突变会导致早衰，这是一种罕见的过早衰老疾病。早衰细胞的主要病理标志是与核层中A型和B型层蛋白的重新分布有关的核变形或气泡。但是，这些与衰老相关的气泡的功能重要性仍然未知。我们已经进行了分析，从在薄层A / C中携带稀有点突变p.S143F（C428T）的早衰患者的皮肤成纤维细胞中，早衰相关的核小球的结构和功能后果。这些气泡形成的微区缺乏核包膜（NE）/薄层的主要结构成分，包括B型薄层和核孔复合物（NPC），并且富含A型薄层。使用激光捕获显微切割和比较基因组杂交（CGH）分析，我们显示，尽管这些域缺少着丝粒异染色质和染色体的基因贫乏区域，但它们却富含基因富集的染色体区域。与其他转录因子相比，RNA聚合酶II的活性形式也大量富集了气泡以及新生的RNA，但是核共激活因子SKIP的气泡显着减少。我们的结果表明，p.S143F早衰突变不仅对层板的结构有严重影响，而且对相间染色质结构域和转录的组织也有严重影响。这些结构缺陷很可能导致早衰和其他类型的椎间盘疾病中报道的基因表达变化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号