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

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...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2015-01, Vol.43 (2), p.760-774
Main Authors: Rodriguez, Ramon M, Suarez-Alvarez, Beatriz, Mosén-Ansorena, David, García-Peydró, Marina, Fuentes, Patricia, García-León, María J, Gonzalez-Lahera, Aintzane, Macias-Camara, Nuria, Toribio, María L, Aransay, Ana M, Lopez-Larrea, Carlos
Format: Article
Language:English
Subjects:
Cell Differentiation - genetics
DNA Methylation
Gene Expression
Gene Expression Regulation
Gene regulation, Chromatin and Epigenetics
Humans
Receptors, Antigen, T-Cell, alpha-beta - analysis
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymocytes - cytology
Thymus Gland - cytology
Thymus Gland - immunology
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gku1340