Pumfery Anne, Deng Longwen, Maddukuri Anil, de la Fuente Cynthia, Li Hong, Wade John D, Lambert Paul, Kumar Ajit, Kashanchi Fatah
Department of Biochemistry and Molecular Biology, George Washington University, School of Medicine, Washington, DC 20037, USA.
Curr HIV Res. 2003 Jul;1(3):343-62. doi: 10.2174/1570162033485186.
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS. Following entry into the host cell, the viral RNA is reverse transcribed into DNA and subsequently integrated into the host genome as a chromatin template. Chromatin structure may be responsible for silencing retroviral gene expression. Transcriptional activation occurs after ATP-dependent chromatin remodeling complexes alter chromatin structure and positioning of nucleosomes. Histone acetyltransferases (HATs), histone deacetylases (HDACs), kinases, and methyltransferases (HMTs), covalently modify nucleosomes by adding or removing chemical moieties in the N-terminal tails of histones. Recent advances have indicated that HIV-1 encoded proteins interact with chromatin remodeling complexes and histone modifying enzymes, implying that chromatin remodeling plays an important role in the HIV-1 life cycle. Nucleosomes are positioned on the HIV-1 LTR and are barriers to transcription. Following cellular activation, these nucleosomes are modified and repositioned allowing for activation of viral gene expression. Tat recruits various HATs to the HIV-1 promoter region and can also be acetylated by some of these enzymes. Unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin T complexes and facilitates transcription initiation. Acetylated Tat dissociates from the TAR RNA structure and recruits bromodomain-containing chromatin modifying complexes such as p/CAF and SWI/SNF to facilitate transcription elongation. This review summarizes our current knowledge and understanding of chromatin remodeling complexes and their regulation of HIV-1 replication, and highlights the important contributions HIV-1 research has made to further our understanding of the transcription process.
人类免疫缺陷病毒1型（HIV-1）是艾滋病的病原体。进入宿主细胞后，病毒RNA被逆转录为DNA，随后作为染色质模板整合到宿主基因组中。染色质结构可能导致逆转录病毒基因表达沉默。转录激活发生在依赖ATP的染色质重塑复合物改变染色质结构和核小体定位之后。组蛋白乙酰转移酶（HATs）、组蛋白去乙酰化酶（HDACs）、激酶和甲基转移酶（HMTs）通过在组蛋白N端尾部添加或去除化学基团来共价修饰核小体。最近的研究进展表明，HIV-1编码的蛋白质与染色质重塑复合物和组蛋白修饰酶相互作用，这意味着染色质重塑在HIV-1生命周期中起着重要作用。核小体位于HIV-1长末端重复序列（LTR）上，是转录的障碍。细胞激活后，这些核小体被修饰并重新定位，从而激活病毒基因表达。Tat蛋白将各种HATs招募到HIV-1启动子区域，并且它自身也能被其中一些酶乙酰化。未修饰的Tat蛋白参与与CBP/p300和cdk9/细胞周期蛋白T复合物的结合，并促进转录起始。乙酰化的Tat蛋白从TAR RNA结构上解离，并招募含溴结构域的染色质修饰复合物，如p/CAF和SWI/SNF，以促进转录延伸。本综述总结了我们目前对染色质重塑复合物及其对HIV-1复制调控的认识和理解，并强调了HIV-1研究对深化我们对转录过程理解所做出的重要贡献。
