T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer

Title: T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer
Authors: Cobb, BS
Nesterova, TB
Thompson, E
Hertweck, A
O'Connor, E
Godwin, J
Wilson, CB
Brockdorff, N
Fisher, AG
Smale, ST
Merkenschlager, M
Item Type: Journal Article
Abstract: The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA stability, and translation in a wide range of organisms. To provide a model system to explore the role of Dicer-generated RNAs in the differentiation of mammalian cells in vivo, we have generated a conditional Dicer allele. Deletion of Dicer at an early stage of T cell development compromised the survival of alphabeta lineage cells, whereas the numbers of gammadelta-expressing thymocytes were not affected. In developing thymocytes, Dicer was not required for the maintenance of transcriptional silencing at pericentromeric satellite sequences (constitutive heterochromatin), the maintenance of DNA methylation and X chromosome inactivation in female cells (facultative heterochromatin), and the stable shutdown of a developmentally regulated gene (developmentally regulated gene silencing). Most remarkably, given that one third of mammalian mRNAs are putative miRNA targets, Dicer seems to be dispensable for CD4/8 lineage commitment, a process in which epigenetic regulation of lineage choice has been well documented. Thus, although Dicer seems to be critical for the development of the early embryo, it may have limited impact on the implementation of some lineage-specific gene expression programs.
Issue Date: 2-May-2005
Date of Acceptance: 29-Mar-2005
URI: http://hdl.handle.net/10044/1/71594
DOI: https://doi.org/10.1084/jem.20050572
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 1367
End Page: 1373
Journal / Book Title: Journal of Experimental Medicine
Volume: 201
Issue: 9
Copyright Statement: © 2005 Rockefeller University Press.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: PO4050659629
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
DNA METHYLATION
X-INACTIVATION
STEM-CELLS
MICRORNAS
GENES
COMMITMENT
SELECTION
LEUKEMIA
DEATH
DELTA
Animals
Apoptosis
Blotting, Southern
Cell Differentiation
Cells, Cultured
CpG Islands
DNA Methylation
Gene Expression Regulation, Developmental
Heterochromatin
In Situ Hybridization, Fluorescence
Mice
Mice, Transgenic
Reverse Transcriptase Polymerase Chain Reaction
Ribonuclease III
T-Lymphocytes
T-Lymphocytes
Cells, Cultured
Heterochromatin
Animals
Mice, Transgenic
Mice
Ribonuclease III
Blotting, Southern
In Situ Hybridization, Fluorescence
Reverse Transcriptase Polymerase Chain Reaction
Apoptosis
Cell Differentiation
DNA Methylation
Gene Expression Regulation, Developmental
CpG Islands
11 Medical and Health Sciences
Immunology
Conference Place: United States
Online Publication Date: 2005-05-02
Appears in Collections:Clinical Sciences
Molecular Sciences



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