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Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR

Official URL:https://doi.org/10.1038/ni1311
PubMed:View item in PubMed
Creators Name:Bilic, I. and Koesters, C. and Unger, B. and Sekimata, M. and Hertweck, A. and Maschek, R. and Wilson, C.B. and Ellmeier, W.
Journal Title:Nature Immunology
Journal Abbreviation:Nat Immunol
Page Range:392-400
Date:April 2006
Keywords:CD8 Antigens, Chromatin, DNA Methylation, Down-Regulation, Electrophoretic Mobility Shift Assay, Flow Cytometry, Genetic Enhancer Elements, Genetic Epigenesis, Genetic Promoter Regions, Genetic Transcription, Inbred C57BL Mice, Knockout Mice, Neoplasm Proteins, Repressor Proteins, T-Lymphocytes, Animals, Mice
Abstract:Coreceptor expression is tightly regulated during thymocyte development. Deletion of specific Cd8 enhancers leads to variegated expression of CD8αβ heterodimers in double-positive thymocytes. Here we show CD8 variegation is correlated with an epigenetic 'off' state, linking Cd8 enhancer function with chromatin remodeling of the adjacent genes Cd8a and Cd8b1 (Cd8). The zinc finger protein MAZR bound the Cd8 enhancer and interacted with the nuclear receptor corepressor N-CoR complex in double-negative thymocytes. MAZR was downregulated in double-positive and CD8 single-positive thymocytes. 'Enforced' expression of MAZR led to impaired Cd8 activation and variegated CD8 expression. Our results demonstrate epigenetic control of the Cd8 loci and identify MAZR as an important regulator of Cd8 expression. © 2006 Nature Publishing Group.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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