tailieunhanh - Báo cáo y học: "A role for the histone deacetylase HDAC4 in the life-cycle of HIV-1-based vectors"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: A role for the histone deacetylase HDAC4 in the life-cycle of HIV-1-based vectors | Smith et al. Virology Journal 2010 7 237 http content 7 1 237 VIROLOGY JOURNAL RESEARCH Open Access A role for the histone deacetylase HDAC4 in the life-cycle of HIV-1-based vectors Johanna A Smith1 Jennifer Yeung1 Gary D Kao2 René Daniel1 3 4 Abstract HIV-1 integration is mediated by the HIV-1 integrase protein which joins 3 -ends of viral DNA to host cell DNA. To complete the integration process HIV-1 DNA has to be joined to host cell DNA also at the 5 -ends. This process is called post-integration repair PIR . Integration and PIR involve a number of cellular co-factors. These proteins exhibit different degrees of involvement in integration and or PIR. Some are required for efficient integration or PIR. On the other hand some reduce the efficiency of integration. Finally some are involved in integration site selection. We have studied the role of the histone deacetylase HDAC4 in these processes. HDAC4 was demonstrated to play a role in both cellular double-strand DNA break repair and transcriptional regulation. We observed that HDAC4 associates with viral DNA in an integrase-dependent manner. Moreover infection with HIV-1-based vectors induces foci of the HDAC4 protein. The related histone deacetylases HDAC2 and HDAC6 failed to associate with viral DNA after infection. These data suggest that HDAC4 accumulates at integration sites. Finally overexpression studies with HDAC4 mutants suggest that HDAC4 may be required for efficient transduction by HIV-1-based vectors in cells that are deficient in other DNA repair proteins. We conclude that HDAC4 is likely involved in PIR. Introduction Chromatin undergoes expansion and compaction in the course of many fundamental cellular processes including gene expression differentiation cell cycle progression and DNA repair. These alterations of the chromatin structure are largely mediated by histone acetylases and histone deacetylases HDACs . HDACs deacetylate key lysine residues of core histones to induce .