T cell lineage choice and differentiation in the absence of the RNase III enzyme dicer
Author(s)
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.
Date Issued
2005-05-02
Date Acceptance
2005-03-29
Citation
Journal of Experimental Medicine, 2005, 201 (9), pp.1367-1373
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
Medical Research Council (MRC)
Identifier
PII: jem.20050572
Grant Number
PO4050659629
Subjects
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
Coverage Spatial
United States
Date Publish Online
2005-05-02