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首页> 外文学位 >Gene silencing in apoptotic retinal ganglion cells is associated with promoter histone deacetylation and nuclear translocation of HDAC3.
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Gene silencing in apoptotic retinal ganglion cells is associated with promoter histone deacetylation and nuclear translocation of HDAC3.

机译：凋亡的视网膜神经节细胞中的基因沉默与启动子组蛋白去乙酰化和HDAC3的核易位有关。

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摘要

One of the first events in neuronal apoptosis is the silencing of normal gene expression. Although this phenomenon has been well documented in several models of neurodegeneration, little work has been done to examine the mechanism responsible for this widespread downregulation.;There are several types of epigenetic changes that compose the histone code. One epigenetic change often associated with gene silencing is histone deacetylation. The central nervous system neurons, retinal ganglion cells (RGCs), undergo significant decreases in histone acetylation, as well as increases in histone deacetylase (HDAC) activity during apoptosis. These changes begin as early as 1 day post optic nerve crush (ONC) and peak at 5 days post ONC, which is prior to apoptotic cell loss. In addition, there is a sustained increase in the transcript level of Hdac3 followed by the nuclear translocation of HDAC3.;When trichostatin A (TSA), a general HDAC inhibitor, was used to treat RGCs prior to ONC, apoptotic silencing of at least one RGC-specific gene, Fem1c, was prevented. Moreover, the application of TSA was able to attenuate apoptotic loss of RGCs at 2 weeks post ONC.;In addition, similar changes in histone deacetylation and HDAC3 cellular localization were seen in RGCs from mice that develop a chronic glaucomatous condition. Thus, these changes appear to be related to the apoptotic process and are not an aritfact of the crush procedure.
机译：神经元凋亡中的第一个事件之一是正常基因表达的沉默。尽管这种现象已经在几种神经退行性疾病模型中得到了很好的证明，但很少有工作来研究造成这种广泛下调的机制。组蛋白代码由几种表观遗传变化组成。通常与基因沉默相关的一种表观遗传学变化是组蛋白去乙酰化。在凋亡过程中，中枢神经系统神经元视网膜神经节细胞（RGC）经历了组蛋白乙酰化的显着降低，以及组蛋白脱乙酰基酶（HDAC）活性的升高。这些变化最早在视神经挤压（ONC）后1天开始，并在ONC后5天达到高峰，这是在凋亡细胞丢失之前。此外，Hdac3的转录水平会持续增加，然后是HDAC3的核易位。;当使用普通的HDAC抑制剂曲古抑菌素A（TSA）在ONC之前治疗RGC时，至少有一种凋亡RGC特异性基因Fem1c被阻止。此外，TSA的应用能够减轻ONC后2周RGC的细胞凋亡;此外，在患有慢性青光眼疾病的小鼠的RGC中，组蛋白脱乙酰基化和HDAC3细胞定位也发生了类似的变化。因此，这些变化似乎与细胞凋亡过程有关，而不是挤压过程的产物。

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  • 作者

    Pelzel, Heather R.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biology Molecular.;Biology Cell.;Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 233 p.
  • 总页数 233
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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