title: Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes.
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.
authors.affiliation: Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Ubreva
authors.forename: Laura
authors.initials: L
authors.lastname: Ciudad
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Cabrero
authors.forename: Maribel
authors.initials: M
authors.lastname: Parra
authors.forename: Lars H
authors.initials: LH
authors.lastname: Bussmann
authors.forename: Alessandro
authors.initials: A
authors.lastname: di Tullio
authors.forename: Eric M
authors.initials: EM
authors.lastname: Kallin
authors.forename: Jesper
authors.initials: J
authors.lastname: Tegnér
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D054338:Cell Transdifferentiation / Q000235:genetics*; D002478:Cells, Cultured; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D006657:Histones; D050880:p300-CBP Transcription Factors
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