Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes

Javier Rodríguez-Ubreva, Laura Ciudad, David Gómez-Cabrero, Maribel Parra, Lars H. Bussmann, Alessandro Di Tullio, Eric M. Kallin, Jesper Tegnér, Thomas Graf, Esteban Ballestar

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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. © 2011 The Author(s).
Original languageEnglish (US)
Pages (from-to)1954-1968
Number of pages15
JournalNucleic Acids Research
Volume40
Issue number5
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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