Increased expression of the LAZ3 (BCL6) proto-oncogene accompanies murine skeletal myogenesis

The structural alterations of the LAZ3 (BCL6) gene are one of the most freq uent events found in non-Hodgkin lymphoma. LAZ3 encodes a transcriptional r epressor with a POZ/zinc finger structure similar to several Drosophila dev elopment regulators and to the human promyelocytic leukemia-associated PLZF gene. Consistent with the origin of LAZ3-associated malignancies, LAZ3 is expressed in mature B-cells and required for germinal center formation. How ever, its ubiquitous expression, with predominant levels in skeletal muscle , suggests that it may act outside the lymphoid system. To study how LAZ3 c ould be involved in skeletal muscle differentiation, we examined its expres sion in the C2 muscle cells. We report here that LAZ3 is upregulated at bot h mRNA and protein levels during the differentiation of proliferating C2 my oblasts into post-mitotic myotubes. This rise in LAZ3 expression is both pr ecocious and sustained, and is not reversed when myotubes are reexposed to mitogen-rich medium, suggesting that irreversible events occurring upon myo genic terminal differentiation contribute to lock LAZ3 upregulation. Tn add ition, using two different models, we found that a "simple" growth-arrest u pon serum starvation is not sufficient to induce LAZ3 upregulation which ra ther appears as a feature of myogenic commitment and/or differentiation. Fi nally, BrdU incorporation assays in C2 cells entering the differentiation p athway indicate that "high" LAZ3 expression strongly correlates with their exit from the cell cycle. Taken as a whole, these findings suggest that LAZ 3 could play a role in muscle differentiation. Together with some results r eported in other cell types, we propose that LAZ3 may contribute to events common to various differentiation processes, possibly the induction and sta bilization of the withdrawal from the cell cycle.