...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >DNA Methyltransferase 3b Regulates Nerve Growth Factor-Induced Differentiation of PC12 Cells by Recruiting Histone Deacetylase 2
【24h】

DNA Methyltransferase 3b Regulates Nerve Growth Factor-Induced Differentiation of PC12 Cells by Recruiting Histone Deacetylase 2

机译：DNA甲基转移酶3b调节组蛋白脱乙酰基酶2调节神经生长因子诱导的PC12细胞分化。

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

摘要

To elucidate the role of epigenetic reprogramming in cell- or tissue-specific differentiation, we explored the role of DNA methyltransferases (Dnmts) in the nerve growth factor (NGF)-induced differentiation of PC12 (pheochromocytoma) cells into neuronal cells. The mRNA and protein levels of de novo methyltransferase Dnmt3b increased, whereas those of Dnmt3a and Dnmt1 decreased, during NGF-induced neurite outgrowth. Dnmt3b localized in the nucleus, as well as in the growing neurites. When the expression of Dnmt3b was inhibited by antisense or small interfering RNA, PC12 cells continued to proliferate and failed to generate neurites. Cells depleted of Dnmt3b were unable to exit the cell cycle even after 6 days of NGF treatment. Furthermore, this failure in differentiation correlated with significant attenuation in tyrosine phosphorylation of TrkA (a marker for NGF-induced differentiation) and reduced the expression of neuronal markers, Hu antigen, and MAP2. The methyl-CpG content of the PC12 genome or the methylation status of repetitive elements was not significantly altered after differentiation and was not affected by Dnmt3b depletion. This was consistent with the ability of the catalytic-site mutant of Dnmt3b to induce differentiation in Dnmt3b-depleted cells after NGF treatment. The Dnmt3b-mediated differentiation was attributed to its N-terminal domain, which recruits histone deacetylase 2 (Hdac2), as demonstrated by (i) impeding of differentiation by the Hdac inhibitors, (ii) facilitation of the differentiation process by overexpression of the N-terminal domain of Dnmt3b, (iii) higher Hdac activity associated with Dnmt3b after NGF treatment, and (iv) coimmunoprecipitation and cosedimentation of Dnmt3b specifically with Hdac2 in a glycerol density gradient. These data indicate a novel role of Dnmt3b in neuronal differentiation.
机译：为了阐明表观遗传重编程在细胞或组织特异性分化中的作用，我们探讨了DNA甲基转移酶（Dnmts）在神经生长因子（NGF）诱导的PC12（嗜铬细胞瘤）细胞分化为神经元细胞中的作用。在NGF诱导的神经突增生过程中，从头甲基转移酶Dnmt3b的mRNA和蛋白水平增加，而Dnmt3a和Dnmt1的mRNA和蛋白水平降低。 Dnmt3b定位在细胞核以及生长的神经突中。当Dnmt3b的表达被反义或小的干扰RNA抑制时，PC12细胞继续增殖，无法产生神经突。耗尽Dnmt3b的细胞即使经过NGF处理6天也无法退出细胞周期。此外，这种分化失败与TrkA（NGF诱导的分化的标志物）的酪氨酸磷酸化显着减弱有关，并降低了神经元标志物，Hu抗原和MAP2的表达。分化后，PC12基因组的甲基CpG含量或重复元件的甲基化状态没有显着改变，并且不受Dnmt3b消耗的影响。这与在NGF处理后Dnmt3b的催化位点突变体在Dnmt3b耗尽的细胞中诱导分化的能力是一致的。 Dnmt3b介导的分化归因于其N末端结构域，该结构募集了组蛋白脱乙酰基酶2（Hdac2），表现为（i）通过Hdac抑制剂阻止分化，（ii）通过N的过表达促进分化过程-Dnmt3b的末端结构域，（iii）NGF处理后与Dnmt3b相关的Hdac活性更高，以及（iv）Dnmt3b与甘油Hdac2在甘油密度梯度中共免疫沉淀和共沉淀。这些数据表明Dnmt3b在神经元分化中的新作用。

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