NF-M (CHICKEN C EBP-BETA) INDUCES EOSINOPHILIC DIFFERENTIATION AND APOPTOSIS IN A HEMATOPOIETIC PROGENITOR-CELL LINE/

CAAT/enhancer binding proteins (C/EBPs) are transcriptional activators implicated in the differentiation processes of various cell lineages. We have shown earlier that NF-M, the chicken homolog of C/EBP beta, i s specifically expressed in myelomonocytic and eosinophilic cells of t he hematopoietic system. To investigate the role of NF-M in hematopoie tic cell lineage commitment, we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrog en receptor. This construct was stably expressed in a multipotent prog enitor cell line transformed by the Myb-Ets oncoprotein. We report her e that both NF-M-dependent promoter constructs and resident genes coul d be activated by addition of beta-estradiol to the NF-M-estrogen rece ptor expressing progenitors. At the same time, we observed a downregul ation of progenitor-specific surface markers and the up-regulation of differentiation markers restricted to the eosinophil and myeloid linea ges. In addition to the onset of differentiation, cell death was induc ed with typical apoptotic features. Our results suggest that NF-M play s an important role in commitment along the eosinophil lineage and in the induction of apoptosis.