SUMOylation interferes with CCAAT/enhancer-binding protein β-mediated c-myc repression, but not IL-4 activation in T cells

The transcription factor C/EBP beta transactivates the IL-4 gene in murine T lymphocytes and facilitates Th2 cell responses. In this study, we demonstrate that C/EBP beta also acts as a repressor of T cell proliferation. By binding to the c-myc promoter(s), C/EBP beta represses c-Myc expression and, therefore, arrests T cells in the G(1) phase of the cell cycle. For C/EBP beta-mediated repression, the integrity of its N-terminal transactivation domain is essential whereas the central regulatory domain is dispensable. This central regulatory domain is sumoylated in vivo which leads to an alteration of the activity of C/EBP beta. Whereas sumoylation does not affect the C/EBP beta-mediated activation of the IL-4 gene, it relieves its repressive effect on c-Myc expression and T cell proliferation. Similar to several other transcription factors, sumoylation redistributes nuclear C/EBP beta and targets it to pericentric heterochromatin. These results suggest an important role of sumoylation in adjusting the finely tuned balance between proliferation and differentiation in peripheral T cells which is controlled by C/EBP beta.