NDLI: T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer

Content Provider	PubMed Central
Author	Cobb, Bradley S. Nesterova, Tatyana B. Thompson, Elizabeth Hertweck, Arnulf O'connor, Eric Godwin, Jonathan Wilson, Christopher B. Brockdorff, Neil Fisher, Amanda G. Smale, Stephen T. Matthias, Merkenschlager
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 αβ lineage cells, whereas the numbers of γδ-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.
Related Links	http://dx.doi.org/10.1084/jem.20050572
Ending Page	1373
Page Count	7
Starting Page	1367
File Format	PDF
ISSN	00221007
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	9
Volume Number	201
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2005-05-02
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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