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首页|richostatin A对鸡胚翅芽发生中基因表达模式的作用

richostatin A对鸡胚翅芽发生中基因表达模式的作用

richostatin A affects gene expression patterns during growth of chick wing buds

中文摘要英文摘要

表遗传修饰和染色质结构重组(chromatin remodelling)参与了胚胎形成及肿瘤发生,乙酰化作用(acetylation)是调控基因转录的关键修饰之一,组蛋白去乙酰基酶抑制剂被视为肿瘤治疗中最有前景的药物开发目标。然而,哪些基因在体内对乙酰化作用修饰更敏感?这些基本问题仍未完全知晓。我们以鸡胚翅芽作为实验模型,用HDAC抑制剂-Trichostatin A (TSA)处理翅芽,研究翅芽发生中一系列基因对TSA的反应。结果显示,TSA (75 µM)能够改变某些对翅芽发育具有重要功能的基因的表达水平,其中,SF/HGF 和 Twist1基因的表达被上调;FGF8、Shh、TCF4、Myf5 及 MyoD基因的表达被下调;与此不同,Pax3、 Paraxis、CREB和 PCNA基因的表达水平不受TSA作用的影响。结果提示,发育的鸡胚翅芽能够作为一个便利的、供体内研究HDACs抑制剂对基因表达作用的模型,有助于提高我们对染色质结构重组和表观遗传对基因表达的调控作用,以及对正在开发的抗癌药物的认识。

Epigenetic controlling and chromatin remodelling are involved in embryonic genesis and tumorigenesis. Acetylation is one of the key modifications to control gene transcription. HDACs inhibitor is considered to be among the most promising targets in drug development for cancer therapy. However, that basic aspects of what kinds of genes are more sensitive to the modification of acetylation in vivo are not fully understood. Taking chicken embryonic limb as an experimental model, the reaction of a batch of genes has been investigated in the limbs treated with Trichostatin A (TSA), a histone deacetylase (HDAC)-inhibitor. The results show that TSA (75 µM) changes the expression levels of the genes, which have important functions during limb development. Among them, SF/HGF and Twist1 were up-regulated, and FGF8, Shh, TCF4, Myf5 and MyoD were down-regulated. In contrast to that, the Pax3, Paraxis, CREB, and PCNA were still expressed at the same levels. Chicken limb development can be served as a convenient model in vivo for studying the effect of HDAC inhibitors on gene expression. It may be useful for improving our understanding of the role of chromatin remodelling and epigenetic control of gene expression patterns and developing the drugs against cancer.

戴方平、赵望泓、王建林、Beate Brand-Saberi

基础医学生物科学研究方法、生物科学研究技术分子生物学

去乙酰化酶抑制剂,基因表达,翅芽发育,Trichostation A,鸡胚

eacetylase inhibitor Gene expression Limb development Trichostation A Chick embryo in vivo

戴方平,赵望泓,王建林,Beate Brand-Saberi.richostatin A对鸡胚翅芽发生中基因表达模式的作用[EB/OL].(2007-07-04)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/200707-78.点此复制

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