HDAC inhibitors stimulate viral transcription by multiple mechanisms.
HDAC inhibitors stimulate viral transcription by multiple mechanisms.
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DOI：
10.1186/1743-422x-5-43
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发表时间：
2008-03-19
期刊：
影响因子：
4.8
通讯作者：
Milavetz B
中科院分区：
文献类型：
--
作者：
Balakrishnan L;Milavetz B
组蛋白去乙酰化酶抑制剂（HDACi）处理对SV40转录和复制的影响通过监测早期和晚期表达水平、复制程度以及在丁酸钠（NaBu）和曲古斯汀A （TSA）处理后能够转录和复制的SV40小染色体的百分比来确定。研究发现，HDACi处理通过增加携带RNA聚合酶II （RNAPII）转录复合物的小染色体数量和增加RNAPII对转录小染色体的占用，最大程度地刺激了早期转录和晚期转录。HDACi治疗也部分缓解了感染后期t抗原早期转录的正常下调。后期转录小染色体的募集增加与SV40复制的相应减少和能够复制的小染色体的百分比相关。这些结果表明，组蛋白去乙酰化在SV40溶性感染的许多方面的调节中起着关键作用。
The effects of histone deacetylase inhibitor (HDACi) treatment on SV40 transcription and replication were determined by monitoring the levels of early and late expression, the extent of replication, and the percentage of SV40 minichromosomes capable of transcription and replication following treatment with sodium butyrate (NaBu) and trichostatin A (TSA). The HDACi treatment was found to maximally stimulate early transcription at early times and late transcription at late times through increased numbers of minichromosomes which carry RNA polymerase II (RNAPII) transcription complexes and increased occupancy of the transcribing minichromosomes by RNAPII. HDACi treatment also partially relieved the normal down-regulation of early transcription by T-antigen seen later in infection. The increased recruitment of transcribing minichromosomes at late times was correlated to a corresponding reduction in SV40 replication and the percentage of minichromosomes capable of replication. These results suggest that histone deacetylation plays a critical role in the regulation of many aspects of an SV40 lytic infection.