pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes
pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes
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DOI：
10.1242/jcs.078253
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发表时间：
2011-03-15
影响因子：
4
通讯作者：
Nagata, Kyosuke
中科院分区：
文献类型：
--
作者：
Kadota, Shinichi;Nagata, Kyosuke
I型干扰素通过诱导干扰素刺激基因(ISGs)的转录，在建立细胞抗病毒状态中发挥重要作用。一般来说，组蛋白乙酰转移酶(HATS)是转录的正调控因子，但组蛋白脱乙酰酶(HDAC)活性对于ISGs的转录诱导是必不可少的。已知pp32是乙酰基转移酶抑制因子(INHAT)复合体的关键成分，该复合体抑制HAT依赖的转录激活。在这里，我们证明了pp32参与了ISG转录的正向调控。PP32与信号转导和转录激活因子1(STAT1)及信号转导和转录激活因子2(STAT2)以干扰素依赖的方式相互作用。Pp32不是STATS酪氨酸磷酸化和核转位所必需的，而是转录复合体与ISG启动子结合所必需的，从而最大限度地激活转录。在未经干扰素处理的细胞中，PP32与ISG启动子相关，并且其结合量随处理时间的变化而波动。短干扰RNA(SiRNA)介导的pp32表达下调降低了ISG启动子上的组蛋白乙酰化水平，提示pp32通过INHAT以外的功能在ISG转录中发挥作用。综上所述，我们认为pp32参与了ISG转录起始复合体的形成，可能是其招募者。
Type I interferon (IFN) plays a crucial role in establishing the cellular antiviral state by inducing transcription of IFN-stimulated genes (ISGs). Generally, histone acetyltransferases (HATs) are positive regulators of transcription, but histone deacetylase (HDAC) activity is essential for transcriptional induction of ISGs. pp32 is known to be a key component of the inhibitor of acetyltransferase (INHAT) complex that inhibits HAT-dependent transcriptional activation. Here, we show that pp32 is involved in the positive regulation of ISG transcription. pp32 interacted with signal transducer and activator of transcription 1 (STAT1) and STAT2 in an IFN-dependent manner. pp32 was not required for tyrosine phosphorylation and nuclear translocation of STATs, but was needed for binding of transcriptional complexes with ISG promoters and, thereby, for maximal transcription activation. pp32 was found to be associated with ISG promoters in IFN-untreated cells, and its binding amount fluctuated as a function of time after IFN treatment. short interfering RNA (siRNA)mediated knockdown of pp32 expression reduced the histone acetylation level on ISG promoters, suggesting that pp32 plays a role in ISG transcription by a function other than that of INHAT. Taking these findings together, we propose that pp32 is involved in the formation of ISG transcription initiation complexes, possibly as their recruiter.