Transcription factor YY1 interacts with retroviral integrases and facilitates integration of moloney murine leukemia virus cDNA into the host chromosomes.
Retroviral integrases associate during the early viral life cycle with preintegration complexes that catalyze the integration of reverse-transcribed viral cDNA into the host chromosomes. Several cellular and viral proteins have been reported to be incorporated in the preintegration complex. This study demonstrates that transcription factor Yin Yang 1 binds to Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. The results of coimmunoprecipitation and in vitro pulldown assays revealed that Yin Yang 1 interacted with the catalytic core and C-terminal domains of Moloney murine leukemia virus and human immunodeficiency virus type 1 integrases, while the transcriptional repression and DNA-binding domains of the Yin Yang 1 molecule interacted with Moloney murine leukemia virus integrase. Immunoprecipitation of the cytoplasmic fraction of virus-infected cells followed by Southern blotting and chromatin immunoprecipitation demonstrated that Yin Yang 1 associated with Moloney murine leukemia virus cDNA in virus-infected cells. Yin Yang 1 enhanced the in vitro integrase activity of Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. Furthermore, knockdown of Yin Yang 1 in host cells by small interfering RNA reduced Moloney murine leukemia virus cDNA integration in vivo, although viral cDNA synthesis was increased, suggesting that Yin Yang 1 facilitates integration events in vivo. Taking these results together, Yin Yang 1 appears to be involved in integration events during the early viral life cycle, possibly as an enhancer of integration.
Inayoshi
Yujin
Y
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. inayoshi@nubio.nagoya-u.ac.jp
Okino
Yuuki
Y
Miyake
Katsuhide
K
Mizutani
Akifumi
A
Yamamoto-Kishikawa
Junko
J
Kinoshita
Yuya
Y
Morimoto
Yusuke
Y
Imamura
Kazuhito
K
Morshed
Mahboob
M
Kono
Ken
K
Itoh
Toshinari
T
Nishijima
Ken-ichi
K
Iijima
Shinji
S
D001358:Avian Sarcoma Viruses / Q000201:enzymology; D002458:Cell Fractionation; D018076:DNA, Complementary / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D047468:Immunoprecipitation; D019426:Integrases / Q000378:metabolism*; D008979:Moloney murine leukemia virus / Q000201:enzymology* / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014764:Viral Proteins / Q000378:metabolism*; D016662:Virus Integration; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D004279:DNA, Viral; D014764:Viral Proteins; D050986:YY1 Transcription Factor; D019426:Integrases