Sadowski Ivan, Lourenco Pedro, Malcolm Tom
Department of Biochemistry and Molecular Biology, Molecular Epigenetics, LSI, University of British Columbia, 2350 Health Sciences Mall, Vancouver, Canada.
Curr HIV Res. 2008 Jun;6(4):286-95. doi: 10.2174/157016208785132563.
Transcription of the integrated HIV provirus is subject to regulation by chromatin organization and must employ host cell transcription factors and chromatin modifying complexes to promote the formation of latency, and then reverse this process to replicate in response to T cell activation. The repressed latent HIV-1 proviral 5' LTR is organized into a defined structure where two de-acetylated and positioned nucleosomes flank the enhancer region, presumably imposing a block to transcriptional initiation and elongation. LTR-associated nucleosomes undergo further histone H3 K9 trimethylation, to cause silencing by recruitment of HP1. In this article, we review current understanding of how the transcriptionally silenced provirus might be established through the function of transcription factors that bind conserved cis-elements, including SP1, YY1, NF-kappaB, CBF-1 and RBF-2 (USF/TFII-I), and propose mechanisms by which factors bound to the repressed LTR can enable reactivation in response to cell signaling.
整合的HIV前病毒的转录受到染色质组织的调控,必须利用宿主细胞转录因子和染色质修饰复合物来促进潜伏期的形成,然后逆转这一过程以响应T细胞激活进行复制。被抑制的潜伏HIV-1前病毒5' LTR被组织成一种特定结构,其中两个去乙酰化且定位的核小体位于增强子区域两侧,推测这对转录起始和延伸形成了阻碍。与LTR相关的核小体经历进一步的组蛋白H3 K9三甲基化,通过招募HP1导致沉默。在本文中,我们综述了目前对转录沉默的前病毒如何通过结合保守顺式元件的转录因子(包括SP1、YY1、NF-κB、CBF-1和RBF-2(USF/TFII-I))的功能而建立的理解,并提出了与被抑制的LTR结合的因子能够响应细胞信号实现重新激活的机制。