The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic 
differentiation and the formation of myeloid malignancies when mutated. An ideal 
system to study the role of Tet2 in myelopoeisis is CEBPα-induced 
transdifferentiation of pre-B cells into macrophages. Here we found that CEBPα 
binds to upstream regions of Tet2 and that the gene becomes activated. Tet2 
knockdowns impaired the upregulation of macrophage markers as well as phagocytic 
capacity, suggesting that the enzyme is required for both early and late stage 
myeloid differentiation. A slightly weaker effect was seen in primary cells with 
a Tet2 ablation. Expression arrays of transdifferentiating cells with Tet2 
knockdowns permitted the identification of a small subset of myeloid genes whose 
upregulation was blunted. Activation of these target genes was accompanied by 
rapid increases of promoter hydroxy-methylation. Our observations indicate that 
Tet2 helps CEBPα rapidly derepress myeloid genes during the conversion of pre-B 
cells into macrophages.