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PMID: 20383150 Published · ppublish English Journal Article

The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes.

Nature immunology ·Vol. 11 ·No. 5 ·2010-05-00 ·Pages 442-8

Sakaguchi S, Hombauer M, Bilic I, Naoe Y, Schebesta A, Taniuchi I, Ellmeier W

Abstract

The CD4 versus CD8 lineage specification of thymocytes is linked to coreceptor expression. The transcription factor MAZR has been identified as an important regulator of Cd8 expression. Here we show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR negatively regulates the Cd8 loci during the transition to the double-positive (DP) stage. Moreover, loss of MAZR led to partial redirection of major histocompatibility complex (MHC) class I-restricted thymocytes into CD4(+) helper-like T cells, which correlated with derepression of Th-POK, a central transcription factor for helper-lineage development. MAZR bound the silencer of the gene encoding Th-POK, which indicated direct regulation of this locus by MAZR. Thus, MAZR is part of the transcription factor network that regulates the CD8 lineage differentiation of DP thymocytes.

MeSH Terms
Animals Bone Marrow Transplantation CD4 Antigens/genetics,metabolism CD4-Positive T-Lymphocytes/cytology,immunology,metabolism CD8 Antigens/genetics,metabolism CD8-Positive T-Lymphocytes/cytology,immunology,metabolism Cell Differentiation/genetics,immunology Cell Lineage/genetics,immunology Cell Transdifferentiation/genetics,immunology Cells, Cultured Gene Regulatory Networks H-2 Antigens/genetics,metabolism Lymphopoiesis/genetics Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neoplasm Proteins/genetics,immunology,metabolism Protein Binding/genetics,immunology Radiation Chimera Receptors, Antigen, T-Cell/genetics,metabolism Repressor Proteins/genetics,immunology,metabolism Silencer Elements, Transcriptional/immunology Transcription Factors/genetics,metabolism Transcriptional Activation/genetics,immunology
Chemicals
CD4 Antigens CD8 Antigens H-2 Antigens Neoplasm Proteins Receptors, Antigen, T-Cell Repressor Proteins Th-POK protein, mouse Transcription Factors Zfp278 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sakaguchi Shinya
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Hombauer Matthias
Bilic Ivan
Naoe Yoshinori
Schebesta Alexandra
Taniuchi Ichiro
Ellmeier Wilfried
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1860
Published
2010-05-00
Epub
2010-00-11
Pages
442-8
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3365445
Subset
IM
Grants
Austrian Science Fund FWF · P 19930 · Austria
Austrian Science Fund FWF · Y 163 · Austria
Corrections
CommentIn
PMID: 20404849
External Links
PubMed source DOI: 10.1038/ni.1860 PMC Full Text View journal details
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