A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.
The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development. Deletion of Dnmt1 in early double-negative thymocytes led to impaired survival of TCRalphabeta(+) cells and the generation of atypical CD8(+)TCRgammadelta(+) cells. Deletion of Dnmt1 in double-positive thymocytes impaired activation-induced proliferation but differentially enhanced cytokine mRNA expression by naive peripheral T cells. We conclude that Dnmt1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells.
Pubmed ID: 11728338 RIS Download
Animals | Cell Differentiation | Cell Lineage | DNA (Cytosine-5-)-Methyltransferase | DNA Methylation | Gene Expression Regulation | Mice | Mice, Transgenic | T-Lymphocytes