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.

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.

• Authors: A Hasegawa, M Yasukawa, I Sakai, S Fujita
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 2 Pg. 1125-31 (Jan 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11145693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Basic-Leucine Zipper Transcription Factors
• DNA-Binding Proteins
• Erythroid-Specific DNA-Binding Factors
• MAX protein, human
• MXD1 protein, human
• Myc associated factor X
• Proto-Oncogene Proteins c-myc
• Receptors, CXCR4
• Repressor Proteins
• Transcription Factors
• YY1 Transcription Factor
• YY1 protein, human
• DNA

Topics

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Basic-Leucine Zipper Transcription Factors
• CD4-Positive T-Lymphocytes (metabolism, virology)
• Cell Line
• DNA (metabolism)
• DNA-Binding Proteins (antagonists & inhibitors, biosynthesis, genetics, metabolism)
• Down-Regulation (genetics, immunology)
• Erythroid-Specific DNA-Binding Factors
• Genetic Vectors (immunology, metabolism)
• Herpesvirus 6, Human (genetics, immunology)
• Humans
• Promoter Regions, Genetic (immunology)
• Protein Binding (genetics, immunology)
• Proto-Oncogene Proteins c-myc (antagonists & inhibitors, metabolism)
• Receptors, CXCR4 (antagonists & inhibitors, biosynthesis, genetics)
• Repressor Proteins (antagonists & inhibitors, biosynthesis, genetics, metabolism)
• Transcription Factors (antagonists & inhibitors, biosynthesis, genetics, metabolism)
• Transcription, Genetic (immunology)
• Transfection
• YY1 Transcription Factor