HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition
HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition
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DOI：
10.1128/mcb.25.14.6140-6153.2005
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Stein, GS
中科院分区：
文献类型：
--
作者：
Miele, A;Braastad, CD;Stein, GS
真核细胞中的基因组复制需要组蛋白生物合成与 G(1)/S 相转变时 DNA 复制开始的严格耦合。一个基本问题是将 G 后期的限制性 (R) 点与 S 期开始时的组蛋白基因表达联系起来的机制。在这里，我们证明 HiNF-P（复制依赖性组蛋白 H4 基因的转录调节因子）直接与细胞周期蛋白 E/CDK2 的底物 p220（NPAT）相互作用，在 S 期共激活组蛋白基因。 HiNF-P 和 p220 以细胞周期依赖性方式靶向并共定位于龈灶（Cajal 小体）。 HiNF-P/p220 相互作用的遗传或生化破坏会损害 G(1)/S 相转变时组蛋白 H4 基因的激活，并阻碍细胞周期进程。我们的结果表明，HiNF-P 和 p220 形成一个关键的调控模块，将 G(1)/S 相转变的组蛋白 H4 基因表达与 R 点的细胞周期蛋白 E/CDK2 信号通路直接连接起来。
Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G(1)/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G, with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220(NPAT), a substrate of cyclin E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted to, and colocalize at, sulmuclear foci (Cajal bodies) in a cell cycle-dependent manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction compromises histone H4 gene activation at the G(1)/S phase transition and impedes cell cycle progression. Our results show that HiNF-P and p220 form a critical regulatory module that directly links histone H4 gene expression at the G(1)/S phase transition to the cyclin E/CDK2 signaling pathway at the R point.