title: A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival.
abstract: 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.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Lee
authors.forename: D R
authors.initials: DR
authors.lastname: Fitzpatrick
authors.forename: C
authors.initials: C
authors.lastname: Beard
authors.forename: H K
authors.initials: HK
authors.lastname: Jessup
authors.forename: S
authors.initials: S
authors.lastname: Lehar
authors.forename: K W
authors.initials: KW
authors.lastname: Makar
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Melgosa
authors.forename: M T
authors.initials: MT
authors.lastname: Sweetser
authors.forename: M S
authors.initials: MS
authors.lastname: Schlissel
authors.forename: S
authors.initials: S
authors.lastname: Nguyen
authors.forename: S R
authors.initials: SR
authors.lastname: Cherry
authors.forename: J H
authors.initials: JH
authors.lastname: Tsai
authors.forename: S M
authors.initials: SM
authors.lastname: Tucker
authors.forename: W M
authors.initials: WM
authors.lastname: Weaver
authors.forename: A
authors.initials: A
authors.lastname: Kelso
authors.forename: R
authors.initials: R
authors.lastname: Jaenisch
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse