Expression of cyclin D2 in Epstein-Barr virus-positive Burkitt's lymphoma cell lines is related to methylation status of the gene.
The cyclin D2 gene is not expressed in resting primary B lymphocytes or in group I Burkitt's lymphoma (BL) cell lines that retain the characteristics of authentic BL cells. Expression of cyclin D2 is induced in primary B lymphocytes following infection with Epstein-Barr virus (EBV) or transfection of the EBV genes EBNA-LP and EBNA-2. However, attempts to induce cyclin D2 expression in BL cell lines by the enforced expression of EBV genes were unsuccessful. Since the demethylation agent 5-azacytidine has been shown to modulate viral gene expression in BL cells, we explored the possibility that methylation plays a significant role in the control of cyclin D2 expression. We show that 5-azacytidine treatment of the Mutu CI 179 BL cell line led to expression of cyclin D2 RNA and that expression correlated with differences in the methylation status of a CCGG restriction enzyme site near the transcription initiation region of the cyclin D2 gene. Thus, methylation appears to play a direct role in the regulation of the cyclin D2 locus in BL.
Sinclair
A J
AJ
Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, United Kingdom.
Palmero
I
I
Holder
A
A
Peters
G
G
Farrell
P J
PJ
D000956:Antigens, Viral / Q000235:genetics; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000821:virology; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D001374:Azacitidine