English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/125392
Título

Regulation of the transcriptional program by DNA methylation during human αβ T-cell development

AutorRodríguez, Ramón M; García-León, María J.; Toribio, María Luisa; López-Larrea, Carlos
Fecha de publicación14-dic-2014
EditorOxford University Press
CitaciónNucleic Acids Research 43: 760- 774 (2014)
Resumen© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Thymocyte differentiation is a complex process involving well-defined sequential developmental stages that ultimately result in the generation of mature T-cells. In this study, we analyzed DNA methylation and gene expression profiles at successive human thymus developmental stages. Gain and loss of methylation occurred during thymocyte differentiation, but DNA demethylation was much more frequent than de novo methylation and more strongly correlated with gene expression. These changes took place in CpG-poor regions and were closely associated with T-cell differentiation and TCR function. Up to 88 genes that encode transcriptional regulators, some of whose functions in T-cell development are as yet unknown, were differentially methylated during differentiation. Interestingly, no reversion of accumulated DNA methylation changes was observed as differentiation progressed, except in a very small subset of key genes (RAG1, RAG2, CD8A, PTCRA, etc.), indicating that methylation changes are mostly unique and irreversible events. Our study explores the contribution of DNA methylation to T-cell lymphopoiesis and provides a fine-scale map of differentially methylated regions associated with gene expression changes. These can lay the molecular foundations for a better interpretation of the regulatory networks driving human thymopoiesis.
URIhttp://hdl.handle.net/10261/125392
DOI10.1093/nar/gku1340
Identificadoresdoi: 10.1093/nar/gku1340
issn: 1362-4962
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
LarreaC_RegulationoftheTranscriptionalProgrambyDNA.pdf5,07 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.