நுண்ணுயிர் & உயிர்வேதியியல் தொழில்நுட்ப இதழ்

சுருக்கம்

Up-Regulation of Lamin A/C Expression in Epstein-Barr Virus Immortalized B Cells and Burkitt Lymphoma Cell Lines of Activated B Cell Phenotype

Ferenc Banati, Anita Koroknai, Kalman Szenthe, Tamas Tereh, Anita Hidasi, Barbara Bankuti, Krisztina Buzas, Frederic Lemnitzer, Zsolt Ruzsics, Susan Szathmary, Hans Wolf, Daniel Salamon, Janos Minarovits and Hans-Helmut Niller

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. Lamin B could be detected in all nucleated cells studied, whereas the lamin A and lamin C isoforms (lamin A/C) encoded by the LMNA gene are co-expressed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA expression in EBV-immortalized B lymphoblastoid cell lines (LCLs) and in a subset of Burkitt lymphoma (BL) lines characterized by an activated B cell phenotype and a unique latent EBV gene expression pattern (latency III). In these cells the first exon of LMNA was hypomethylated and associated with activating histone marks. In contrast, we observed a low level of lamin A/C mRNA expression in EBV negative BL lines and BL lines with a restricted expression of latent EBV products (latency I). Low LMNA promoter activity was associated with hypermethylation of the LMNA first exon. These data suggest a role for EBV latency products in switching on or upregulating the LMNA promoter (LMNAp) in EBV-infected activated B cells in vitro. Lamin A/C may contribute to the establishment of the activated B cell phenotype. Our data also imply a role of LMNA first exon methylation in the silencing of LMNAp.