The coordinated expression of four different CCAAT/enhancer binding proteins (C/EBPs), C/EBPalpha, C/EBPbeta, C/EBPdelta, and C/EBPepsilon constitutes a critical component of the myeloid differentiation program. C/EBPs are modular proteins, consisting of an activation domain, DNA binding domain and leucine zipper dimerization region. Recent studies including the analysis of mice deficient in several C/EBP proteins emphasize the effects of these molecules in hematopoiesis. C/EBPalpha is a master regulator of myeloid progenitors, C/EBPbeta plays an important role in macrophage and B-cell development, C/EBPgamma is involved in B-cell development, and C/EBPdelta is upregulated during myelopoiesis. Furthermore, C/EBPepsilon is a regulator of terminal differentiation of eosinophils and functional maturation of neutrophils. The formation of alternative combinations of tissue-specific and cell-stage specific C/EBP dimers may allow differential regulation of target genes in hematopoietic cells and commitment to distinctive hematopoietic lineages.
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Yamanaka et al. (1998) studied this question.