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.
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.
Hasegawa
A
A
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan.
Yasukawa
M
M
Sakai
I
I
Fujita
S
S
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D050981:Erythroid-Specific DNA-Binding Factors; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology*; D014162:Transfection; D050986:YY1 Transcription Factor
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C499330:MAX protein, human; C079439:MXD1 protein, human; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D019718:Receptors, CXCR4; D012097:Repressor Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D004247:DNA