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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


  • Lee PP
  • Fitzpatrick DR
  • Beard C
  • Jessup HK
  • Lehar S
  • Makar KW
  • PĂ©rez-Melgosa M
  • Sweetser MT
  • Schlissel MS
  • Nguyen S
  • Cherry SR
  • Tsai JH
  • Tucker SM
  • Weaver WM
  • Kelso A
  • Jaenisch R
  • Wilson CB



Publication Data

November 30, 2001

Associated Grants


Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • DNA (Cytosine-5-)-Methyltransferase
  • DNA Methylation
  • Gene Expression Regulation
  • Mice
  • Mice, Transgenic
  • T-Lymphocytes