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Volume 25 Issue 6
December 2010

    Jie CHEN, Yan-mei LI, Jian-feng LI, Long-ding LIU, Yun LIAO, Rui-xiong NA, Jing-jing WANG, Li-chun WANG and Qi-han LI. Transcriptional Regulation by HSV-1 Induced HTRP via Acetylation System[J]. Virologica Sinica, 2010, 25(6): 417-424. doi: 10.1007/s12250-010-3147-8
    Citation: Jie CHEN, Yan-mei LI, Jian-feng LI, Long-ding LIU, Yun LIAO, Rui-xiong NA, Jing-jing WANG, Li-chun WANG, Qi-han LI. Transcriptional Regulation by HSV-1 Induced HTRP via Acetylation System .VIROLOGICA SINICA, 2010, 25(6) : 417-424.  http://dx.doi.org/10.1007/s12250-010-3147-8
    shu

    HSV1感染相关细胞分子HTRP通过乙酰化体系对病毒转录调控的影响?

    cstr: 32224.14.s12250-010-3147-8

    • 中国医学科学院 北京协和医学院 医学生物学研究所, 云南昆明 650118

    • 通讯作者： Qi-han LI*, imbcams.lq@gmail.com
    • 收稿日期： 2010-05-07
      录用日期： 2010-07-28

    • Ⅰ型单纯疱疹病毒(HSV-1)感染KMB-17后诱导的差异基因htrp所编码蛋白HTRP可与去乙酰化转移酶HDAC辅抑制因子复合物mSin3A的组成成分之一SAP30之间发生相互作用。为了进一步揭示HTRP与SAP30相互作用的生物学意义，本实验利用实时荧光定量PCR及双荧光素酶检测系统，证明HTRP对病毒启动子的转录具有抑制作用，其和SAP30共同作用对病毒基因的转录抑制具有协同效应，且这种效应与HDAC的酶活性相关。ChIP实验证明其具体机理是HTRP能够促进HDACs酶活性而增加组蛋白H3分子第14和9位赖氨酸的去乙酰化水平。

    Transcriptional Regulation by HSV-1 Induced HTRP via Acetylation System

    • Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China

    • Corresponding author: Qi-han LI, imbcams.lq@gmail.com
    • Received Date: 07 May 2010
      Accepted Date: 28 July 2010

      Fund Project: the Ph.D. Programs Foundation of Ministry of Education of China 20060023008The National Natural Science Foundation of China 30670094

    • The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells. HTRP was found to interact with SAP30 (mSin3A Association Protein), one of the components of co-repressor complex mSin3A, which is part of the deacetylation transfer enzyme HDAC. To reveal the biological significance of the interaction between HTRP and SAP30, real- time PCR and a dual-luciferase detecting system was used. The results indicate that HTRP could inhibit the transcription of a viral promoter, whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes, and is related to HDAC enzyme activity. ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.
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      3. Kent J R, Zeng P Y, Aatanasiu D, et al. 2004. During lytic infection herpes simplex virus type 1 is associated with histones bearing modification that correlate with active transcription. J Virol, 78 (18): 10178-10186.
          doi: 10.1128/JVI.78.18.10178-10186.2004

      4. Laherty C D, Billin A N, Lavinsky R M, et al. 1998. SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Mol Cell, 2 (1): 33-42.
          doi: 10.1016/S1097-2765(00)80111-2

      5. Li J F, Liu L D, Ma S H, et al. 2004. HTRP-an immediate-early gene product induced by HSV1 infection in human embryo fibroblasts, is involved in cellular co-repressors. J Biochem, 136: 169-176.
          doi: 10.1093/jb/mvh108

      6. Lin R, Noyce R S, Conllins S E, et al. 2004. The Herpes Simplex Virus ICP0 RING Finger Domain Inhibits IRF3-and IRF7-Mediated Activation of Interferon-Stimulated Genes. J Virol, 8 (4): 1675-1684.

      7. Li Q-H, Dong C H, Wang L C, et al. 2000. Early expression of protooncogenes induced by the binding to cells of two viruses. Acta Biochim Biophys, 32: 149-152.

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      12. Viiri K M, Janis J, Siggers T, et al. 2009. DNA-binding and-bending activities of SAP30L and SAP30 are mediated by a Zinc-dependent module and monophosp-hoinositides. Mol Cell Biol, 29 (2): 342-356.
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      14. Watashi K, Hijikata M, Tagawa A, et al. 2003. Modulation of retinoid signaling by a cytoplasmic viral protein via sequestration of Sp110b, a potent trans-criptional corepressor of Retinoic acid receptor, from the nucleus. Mol Cell Biol, 23 (21): 7498-7509.
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      Transcriptional Regulation by HSV-1 Induced HTRP via Acetylation System

        Corresponding author: Qi-han LI, imbcams.lq@gmail.com
      • Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China
      • Received Date: 07 May 2010
      • Accepted Date: 28 July 2010
      Fund Project:  the Ph.D. Programs Foundation of Ministry of Education of China 20060023008The National Natural Science Foundation of China 30670094

      Abstract: The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells. HTRP was found to interact with SAP30 (mSin3A Association Protein), one of the components of co-repressor complex mSin3A, which is part of the deacetylation transfer enzyme HDAC. To reveal the biological significance of the interaction between HTRP and SAP30, real- time PCR and a dual-luciferase detecting system was used. The results indicate that HTRP could inhibit the transcription of a viral promoter, whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes, and is related to HDAC enzyme activity. ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.

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