National Centre for Cell science, University of Pune Campus, Ganeshkhind, Pune 411007, Maharashtra, India.
Virology. 2010 Apr 25;400(1):76-85. doi: 10.1016/j.virol.2010.01.017. Epub 2010 Feb 11.
Nuclear Matrix and MARs have been implicated in the transcriptional regulation of host as well as viral genes but their precise role in HIV-1 transcription remains unclear. Here, we show that >98% of HIV sequences contain consensus MAR element in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces transcriptional silencing by tethering the LTR MAR to nuclear matrix. SMAR1 associated HDAC1-mSin3 corepressor complex is dislodged from the LTR upon cellular activation by PMA/TNFalpha leading to an increase in the acetylation and a reduction in the trimethylation of histones, associated with the recruitment of RNA Polymerase II on the LTR. Overexpression of SMAR1 lead to reduction in LTR mediated transcription, both in a Tat dependent and independent manner, resulting in a decreased virion production. These results demonstrate the role of SMAR1 in regulating viral transcription by alternative compartmentalization of LTR between the nuclear matrix and chromatin.
核基质和 MARs 已被牵连到宿主和病毒基因的转录调控中，但它们在 HIV-1 转录中的具体作用仍不清楚。在这里，我们表明 >98%的 HIV 序列在其启动子中含有 MAR 元件的共识。我们表明，SMAR1 与 LTR MAR 结合，并通过将 LTR MAR 固定在核基质上来增强转录沉默。SMAR1 相关的 HDAC1-mSin3 核心抑制复合物在 PMA/TNFalpha 激活细胞时从 LTR 上脱离，导致组蛋白乙酰化增加和三甲基化减少，与 RNA 聚合酶 II 在 LTR 上的募集有关。SMAR1 的过表达导致 LTR 介导的转录减少，无论是在 Tat 依赖和独立的方式，导致病毒粒子产量减少。这些结果表明，SMAR1 通过 LTR 在核基质和染色质之间的替代区室化来调节病毒转录。
