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Transcriptional Down-Regulation of CXC Chemokine Receptor 4 Induced by Impaired Association of Transcription Regulator YY1 with c-Myc in Human Herpesvirus 6-Infected Cells

Atsuhiko Hasegawa, Masaki Yasukawa, Ikuya Sakai and Shigeru Fujita
J Immunol January 15, 2001, 166 (2) 1125-1131; DOI: https://doi.org/10.4049/jimmunol.166.2.1125
Atsuhiko Hasegawa
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan
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Masaki Yasukawa
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan
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Ikuya Sakai
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan
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Shigeru Fujita
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan
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Abstract

We have recently reported that down-regulation of CXC chemokine receptor (CXCR) 4 in CD4+ T lymphocytes is induced by human herpesvirus (HHV) 6 infection. In this study, we further studied the mechanisms of HHV-6-induced CXCR4 down-regulation, focusing on the regulation of CXCR4 transcription. Down-regulation of CXCR4 transcription was detected in HHV-6A-infected JJHAN and HHV-6B-infected MT-4 cell lines, as we had previously reported for HHV-6-infected peripheral blood CD4+ T lymphocytes. Luciferase assays revealed that a YY1-binding site around −320 relative to the transcription start site is important for down-regulation of CXCR4 transcription in HHV-6-infected cells. The binding activity of YY1, which is a repressor of CXCR4 transcription, to the CXCR4 promoter appeared to significantly increase in HHV-6-infected cells compared with the binding activity in mock-infected cells. Immunoprecipitation assays showed that in HHV-6-infected cells association of c-Myc with YY1 was decreased and that of Max with c-Myc was increased, whereas association of Mad with Max appeared to be decreased. The amounts of each of YY1, c-Myc, Max, and Mad proteins synthesized in cells were not altered by HHV-6 infection. These data indicate that the decreased association of YY1 with c-Myc that is caused by impaired interaction in the c-Myc/Max/Mad network results in increased binding activity of YY1 to the CXCR4 promoter, mediating down-regulation of CXCR4 production in HHV-6-infected cells.

  • Received June 8, 2000.
  • Accepted October 30, 2000.
  • Copyright © 2001 by The American Association of Immunologists
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The Journal of Immunology: 166 (2)
The Journal of Immunology
Vol. 166, Issue 2
15 Jan 2001
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Transcriptional Down-Regulation of CXC Chemokine Receptor 4 Induced by Impaired Association of Transcription Regulator YY1 with c-Myc in Human Herpesvirus 6-Infected Cells
Atsuhiko Hasegawa, Masaki Yasukawa, Ikuya Sakai, Shigeru Fujita
The Journal of Immunology January 15, 2001, 166 (2) 1125-1131; DOI: 10.4049/jimmunol.166.2.1125

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Transcriptional Down-Regulation of CXC Chemokine Receptor 4 Induced by Impaired Association of Transcription Regulator YY1 with c-Myc in Human Herpesvirus 6-Infected Cells
Atsuhiko Hasegawa, Masaki Yasukawa, Ikuya Sakai, Shigeru Fujita
The Journal of Immunology January 15, 2001, 166 (2) 1125-1131; DOI: 10.4049/jimmunol.166.2.1125
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