Transcriptional activation of histone genes requires NPAT-Dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition
Transcriptional activation of histone genes requires NPAT-Dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition
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DOI：
10.1128/mcb.00607-07
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发表时间：
2008-01-01
影响因子：
5.3
通讯作者：
Zhao, Jiyong
中科院分区：
文献类型：
--
作者：
DeRan, Michael;Pulvino, Mary;Zhao, Jiyong
组蛋白亚型的转录激活是协调调节的，并且与S期进入期间DNA复制的开始紧密耦合。这种配位和偶联的潜在分子机制还没有很好地理解。细胞周期蛋白E-Cdk 2底物NPAT在组蛋白基因的转录激活中起重要作用。在这里，我们表明，NPAT相互作用的Tip 60组蛋白乙酰转移酶复合物的组成部分，通过一个新的氨基酸基序，这是功能保守的E2 F和腺病毒E1 A蛋白。此外，我们证明了转化/反式激活结构域相关蛋白（TRRAP）和Tip 60，Tip 60复合物的两个组成部分，与组蛋白基因启动子在G（1）/S-相边界的NPAT依赖的方式。与TRRAP-Tip 60复合物的结合相关，组蛋白基因启动子处的组蛋白H4乙酰化在G（1）/S-相转变时增加，并且这种增加涉及NPAT功能。通过RNA干扰抑制TRRAP或Tip 60表达抑制组蛋白基因活化。因此，我们的数据支持一个模型，其中NPAT招募TRRAP-Tip 60复合物到组蛋白基因启动子，以协调多个组蛋白基因在G（1）/S-相转变期间的转录激活。
Transcriptional activation of histone subtypes is coordinately regulated and tightly coupled with the onset of DNA replication during S-phase entry. The underlying molecular mechanisms for such coordination and coupling are not well understood. The cyclin E-Cdk2 substrate NPAT has been shown to play an essential role in the transcriptional activation of histone genes at the G(1)/S-phase transition. Here, we show that NPAT interacts with components of the Tip60 histone acetyltransferase complex through a novel amino acid motif, which is functionally conserved in E2F and adenovirus E1A proteins. In addition, we demonstrate that transformation/transactivation domain-associated protein (TRRAP) and Tip60, two components of the Tip60 complex, associate with histone gene promoters at the G(1)/S-phase boundary in an NPAT-dependent manner. In correlation with the association of the TRRAP-Tip60 complex, histone H4 acetylation at histone gene promoters increases at the G(1)/S-phase transition, and this increase involves NPAT function. Suppression of TRRAP or Tip60 expression by RNA interference inhibits histone gene activation. Thus, our data support a model in which NPAT recruits the TRRAP-Tip60 complex to histone gene promoters to coordinate the transcriptional activation of multiple histone genes during the G(1)/S-phase transition.