• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Chromatin Immunoprecipitation on Microarray Analysis of Smad2/3 Binding Sites Reveals Roles of ETS1 and TFAP2A in Transforming Growth Factor β Signaling
【24h】

Chromatin Immunoprecipitation on Microarray Analysis of Smad2/3 Binding Sites Reveals Roles of ETS1 and TFAP2A in Transforming Growth Factor β Signaling

机译：Smad2 / 3结合位点的微阵列分析上的染色质免疫沉淀揭示了ETS1和TFAP2A在转化生长因子β信号传导中的作用。

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

摘要

The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor β (TGF-β) signaling from the plasma membrane to the nucleus. Many transcription factors have been shown to cooperate with the Smad2/3 proteins in regulating the transcription of target genes, enabling appropriate gene expression by cells. Here we identified 1,787 Smad2/3 binding sites in the promoter regions of over 25,500 genes by chromatin immunoprecipitation on microarray in HaCaT keratinocytes. Binding elements for the v-ets erythroblastosis virus E26 oncogene homolog (ETS) and transcription factor AP-2 (TFAP2) were significantly enriched in Smad2/3 binding sites, and knockdown of either ETS1 or TFAP2A resulted in overall alteration of TGF-β-induced transcription, suggesting general roles for ETS1 and TFAP2A in the transcription induced by TGF-β-Smad pathways. We identified novel Smad binding sites in the CDKN1A gene where Smad2/3 binding was regulated by ETS1 and TFAP2A. Moreover, we showed that small interfering RNAs for ETS1 and TFAP2A affected TGF-β-induced cytostasis. We also analyzed Smad2- or Smad3-specific target genes regulated by TGF-β and found that their specificity did not appear to be solely determined by the amounts of the Smad2/3 proteins bound to the promoters. These findings reveal novel regulatory mechanisms of Smad2/3-induced transcription and provide an essential resource for understanding their roles.
机译：Smad2和Smad3（Smad2 / 3）蛋白主要参与转化生长因子β（TGF-β）信号从质膜到细胞核的传递。已显示许多转录因子与Smad2 / 3蛋白协同调节靶基因的转录，从而使细胞能够适当表达基因。在这里，我们通过HaCaT角质形成细胞微阵列上的染色质免疫沉淀，在超过25,500个基因的启动子区域中确定了1,787个Smad2 / 3结合位点。 v-ets成红细胞病病毒E26癌基因同源物（ETS）和转录因子AP-2（TFAP2）的结合元件在Smad2 / 3结合位点显着富集，而ETS1或TFAP2A的敲低导致TGF-β-的整体改变诱导转录，提示ETS1和TFAP2A在TGF-β-Smad途径诱导的转录中具有一般作用。我们在 CDKN1A 基因中发现了新的Smad结合位点，其中Smad2 / 3结合受ETS1和TFAP2A调控。此外，我们显示ETS1和TFAP2A的小干扰RNA影响TGF-β诱导的细胞停滞。我们还分析了由TGF-β调控的Smad2或Smad3特异性靶基因，发现它们的特异性似乎并不仅由与启动子结合的Smad2 / 3蛋白的量决定。这些发现揭示了Smad2 / 3诱导的转录的新型调控机制，并为理解其作用提供了必要的资源。

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