Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity
Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity
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DOI：
10.1073/pnas.0400567101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Levy, DE
中科院分区：
文献类型：
--
作者：
Chang, HM;Paulson, M;Levy, DE
组蛋白去乙酰化酶（HDAC）的活性，通常与转录抑制，是必不可少的IFN刺激基因（ISG）的转录诱导。HDAC功能的抑制导致ISG表达的整体受损，对基础表达的影响很小。HDAC功能不是信号转导子和转录激活子酪氨酸磷酸化、核转位或在染色质上组装所必需的，但它是信号转导子和转录激活子反式激活结构域的完全活性所必需的。HDAC功能也是由病毒感染激活的IFN调节因子3转录因子驱动的基因诱导所必需的，并且对于建立针对黄病毒科、弹状病毒科和小核糖核酸病毒科的抗病毒应答是必不可少的。转录激活中HDAC功能的需求可能代表了快速刺激ISG转录的一般机制。
Histone deacetylase (HDAC) activity, commonly correlated with transcriptional repression, was essential for transcriptional induction of IFN-stimulated genes (ISG). Inhibition of HDAC function led to global impairment of ISG expression, with little effect on basal expression. HDAC function was not required for signal transducer and activator of transcription tyrosine phosphorylation, nuclear translocation, or assembly on chromatin, but it was needed for full activity of the signal transducer and activator of transcription transactivation domain. HDAC function was also required for gene induction driven by the IFN regulatory factor 3 transcription factor activated by virus infection, and it was essential for establishment of an antiviral response against Flaviviridae, Rhabdoviridae, and Picornaviridae. Requirement for HDAC function in transcriptional activation may represent a general mechanism for rapid stimulation of ISG transcription.