Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes
| Autor: | David Gomez-Cabrero, Javier Rodríguez-Ubreva, Maribel Parra, Eric M. Kallin, Lars H. Bussmann, Alessandro di Tullio, Esteban Ballestar, Thomas Graf, Jesper Tegnér, Laura Ciudad |
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| Rok vydání: | 2011 |
| Předmět: |
Cèl·lules B
Cellular differentiation ADN Gene Regulation Chromatin and Epigenetics Biology Epigenesis Genetic Histones Mice 03 medical and health sciences 0302 clinical medicine Epigenetics of physical exercise CCAAT-Enhancer-Binding Protein-alpha Genetics Animals p300-CBP Transcription Factors Epigenetics Promoter Regions Genetic Cells Cultured 030304 developmental biology B cells 0303 health sciences Macrophages Precursor Cells B-Lymphoid Transdifferentiation Promoter DNA DNA Methylation Molecular biology 3. Good health 030220 oncology & carcinogenesis Cell Transdifferentiation DNA methylation Reprogramming |
| Zdroj: | Nucleic Acids Research Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkr1015 |
| Popis: | 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/EBP alpha-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/EBP alpha 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. |
| Databáze: | OpenAIRE |
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