Daxx interacts with HIV-1 integrase and inhibits lentiviral gene expression.
The death-associated protein Daxx is a ubiquitously expressed gene in mammals and is widely involved in transcriptional regulation and cellular intrinsic immune response against incoming virus. We found here that knocking down endogenous Daxx with specific siRNA increased HIV-1-derived lentiviral reporter gene expression in 293T cells. This repressive effect of Daxx is not due to its inhibition on viral gene integration into the cellular genome and is independent of the ubiquitin promoter on the vFUGW lentiviral vector. Instead, this inhibition is dependent on Daxx's interaction with HIV-1 integrase. A histone deacetylases (HDACs) inhibitor increased reporter gene expression to the level similar to Daxx knockdown in vFUGW infected cells but there was no additive effect in combination of HDACs inhibitor and Daxx-specific siRNA. Our results suggest that Daxx may associate with HIV-1-derived lentiviral DNA via interacting with HIV-1 integrase and recruit HDACs to viral DNA to repress lentiviral gene expression.
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
Lu
L
Huang
Guan-lan
GL
Xu
Jian-qi
JQ
Zhang
Ling
L
Tian
Jing-lun
JL
Xue
Jin-zhong
JZ
Chen
William
W
Jia
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D056970:Co-Repressor Proteins; D004279:DNA, Viral / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D004279:DNA, Viral; D056572:Histone Deacetylase Inhibitors; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D019427:HIV Integrase; D006655:Histone Deacetylases; C514801:p31 integrase protein, Human immunodeficiency virus 1