title: ZNF10 inhibits HIV-1 LTR activity through interaction with NF-κB and Sp1 binding motifs.
abstract: Kruppel-associated box-containing zinc finger (KRAB-ZNF) genes constitute the single largest gene family of transcriptional repressors in the genomes of higher organisms. In this study, we isolated 52 cDNA clones of KRAB-ZFPs from U1 cell lines and screened them to identify which were capable of regulating HIV-1 gene expression. We identified 5 KRAB-ZFPs that suppressed ⩾50% of HIV-1 LTR. Of the 5 identified KRAB-ZFPs, the expression of ZNF10 significantly enhanced the transcriptional repression activity of the LTR compared with other ZNFs. In addition, the depletion of endogenous ZNF10 led to the activation of HIV-1 LTR. The repressor activity of ZNF10 was required for TRIM28, SETDB1 and HP1-gamma binding. These results indicate that ZNF10 could be involved in a potent intrinsic antiretroviral defense.
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan. Electronic address: lbnishitsuji@hospk.ncgm.go.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nishitsuji
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors.forename: Leila
authors.initials: L
authors.lastname: Sawada
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sugiyama
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Research Institute, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan. Electronic address: hiroshi.takaku@it-chiba.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: D001665:Binding Sites; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; C109484:ZNF10 protein, human
keywords: HIV-1 LTR; HP1-gamma; KRAB domain; SETDB1; TRIM28; Zinc finger protein