厦门大学药学院周强教授研究组发表艾滋病基因转录调控...

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http://www.bio1000.com/gnjz/immunology/504314.html

2015年5月24日，国际学术期刊《Nucleic Acids Research》(影响因子9.1)在线发表了周强教授课题组的科研论文：“Gene target specificity of the Super Elongation Complex (SEC) family: How HIV-1 Tat employs selected SEC members to activate viral transcription”。

周强教授课题组一直致力于艾滋病基因转录调控的研究，并在该领域取得了多项重大研究成果。超级转录延伸复合体(SEC)对HIV-1和真核细胞基因的转录延伸都有很强的激活作用， AFF1和AFF4可作为募集SEC组分的一个支架。它们可形成牢固的二聚体存在于SEC组分中，但是他们在体内的功能以及功能是否相似犹未可知。该研究首次发现AFF1 和 AFF4存在于具有不同靶基因特异性的单独SEC组分中;以及他们对 HIV-1病毒蛋白Tat的转录激活作用的不同之处。研究结果显示，AFF1- SEC 和 AFF4-SEC的基因调节大部分都没有重叠性，各自行使着不同的功能。

该研究详细阐述了HIV-1病毒蛋白如何使用选定的SEC成员激活病毒转录，为进一步揭示艾滋病病毒HIV的分子病毒机制提供了重要依据,为寻找对抗艾滋病病毒HIV的机理及药物具有重要的理论和实践意义。

原文摘要：

GENE target specificity of the Super Elongation Complex (SEC) family: how HIV-1 Tat employs selected SEC members to activate viral transcription

原文摘要：

The AF4/FMR2 proteins AFF1 and AFF4 act as a scaffold to assemble the Super Elongation Complex (SEC) that strongly activates transcriptional elongation of HIV-1 and cellular genes. Although they can dimerize, it is unclear whether the dimers exist and function within a SEC in vivo. Furthermore, it is unknown whether AFF1 and AFF4 function similarly in mediating SEC-dependent activation of diverse genes. Providing answers to these questions, our current study shows that AFF1 and AFF4 reside in separate SECs that display largely distinct gene target specificities. While the AFF1-SEC is more potent in supporting HIV-1 transactivation by the viral Tat protein, the AFF4-SEC is more important for HSP70 induction upon heat shock. The functional difference between AFF1 and AFF4 in Tat-transactivation has been traced to a single amino acid variation between the two proteins, which causes them to enhance the affinity of Tat for P-TEFb, a key SEC component, with different efficiency. Finally, genome-wide analysis confirms that the genes regulated by AFF1-SEC and AFF4-SEC are largely non-overlapping and perform distinct functions. Thus, the SEC represents a family of related complexes that exist to increase the regulatory diversity and gene control options during transactivation of diverse cellular and viral genes.

doi: 10.1093/nar/gkv541