ZNF10 inhibits HIV-1 LTR activity through interaction with NF-κB and Sp1 binding motifs

Hironori Nishitsuji; Leila Sawada; Ryuichi Sugiyama; Hiroshi Takaku

doi:10.1016/j.febslet.2015.06.013

ZNF10 inhibits HIV-1 LTR activity through interaction with NF-κB and Sp1 binding motifs

FEBS Lett. 2015 Jul 8;589(15):2019-25. doi: 10.1016/j.febslet.2015.06.013. Epub 2015 Jun 19.

Authors

Hironori Nishitsuji¹, Leila Sawada², Ryuichi Sugiyama³, Hiroshi Takaku⁴

Affiliations

¹ 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.
² Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
³ 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.
⁴ 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.

PMID: 26096782
DOI: 10.1016/j.febslet.2015.06.013

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.

Keywords: HIV-1 LTR; HP1-gamma; KRAB domain; SETDB1; TRIM28; Zinc finger protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Gene Expression Regulation, Viral
Genes, Viral
HEK293 Cells
HIV Long Terminal Repeat / physiology*
HIV-1 / genetics*
Humans
Kruppel-Like Transcription Factors / physiology*
NF-kappa B / metabolism*
Repressor Proteins / physiology*
Sp1 Transcription Factor / metabolism*

Substances

Kruppel-Like Transcription Factors
NF-kappa B
Repressor Proteins
Sp1 Transcription Factor
ZNF10 protein, human