Transcription factor-induced lineage reprogramming or transdifferentiation 
experiments are essential for understanding the plasticity of differentiated 
cells. These experiments helped to define the specific role of transcription 
factors in conferring cell identity and played a key role in the development of 
the regenerative medicine field. We here investigated the acquisition of DNA 
methylation changes during C/EBPα-induced pre-B cell to macrophage 
transdifferentiation. Unexpectedly, cell lineage conversion occurred without 
significant changes in DNA methylation not only in key B cell- and 
macrophage-specific genes but also throughout the entire set of genes 
differentially methylated between the two parental cell types. In contrast, 
active and repressive histone modification marks changed according to the 
expression levels of these genes. We also demonstrated that C/EBPα and RNA Pol 
II are associated with the methylated promoters of macrophage-specific genes in 
reprogrammed macrophages without inducing methylation changes. Our findings not 
only provide insights about the extent and hierarchy of epigenetic events in 
pre-B cell to macrophage transdifferentiation but also show an important 
difference to reprogramming towards pluripotency where promoter DNA 
demethylation plays a pivotal role.