Dnmt3a and Dnmt3b in Epidermal Homeostasis and Cancer Progression
DNA methylation is an essential epigenetic mechanism that regulates gene expression. While DNA methylation dynamics during embryonic formation is fairly well understood, its role in adult tissues is still under investigation. Prior to starting my PhD work, we found that the two de novo DNA methyltra...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/456683 |
| Acceso en línea: | http://hdl.handle.net/10803/456683 |
| Access Level: | acceso abierto |
| Palabra clave: | Dnmt3a Dnmt3b Adult stem cells Enhancers DNA methylation Cáncer de piel Células madre de la piel Metilación e ADN Epigenética Mecanismos trascripcionales 616 |
| Sumario: | DNA methylation is an essential epigenetic mechanism that regulates gene expression. While DNA methylation dynamics during embryonic formation is fairly well understood, its role in adult tissues is still under investigation. Prior to starting my PhD work, we found that the two de novo DNA methyltransferases Dnmt3a and Dnmt3b were differentially expressed during epidermal stem cell differentiation. Interestingly, their expression patterns were completely opposite. We thus decided to further investigate the role of DNA methylation, and specifically of Dnmt3a and Dnmt3b, during the process of human epidermal stem cell differentiation. To characterize the epigenomic importance of Dnmt3a and Dnmt3b, we performed several next generation sequencing (NGS) experiments in primary human epidermal stem cells, which mimic faithfully the in vivo patterns of human epidermal cells. To gain insights into the epidermal roles of Dnmt3a and Dnmt3b in an in vivo setting, we generated a conditional epidermal knockout for either protein. We obtained interesting results that complemented and expanded the genomic data obtained from the human stem cell project, with Dnmt3a and Dnmt3b found to locate to several chromatin regions that are essential for both the self-renewal and the proper differentiation of adult stem cells |
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