Journal
NATURE IMMUNOLOGY
Volume 7, Issue 4, Pages 392-400Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1311
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Funding
- Austrian Science Fund FWF [Y 163] Funding Source: Medline
- NICHD NIH HHS [HD18184, R01 HD039454, HD39454, R01 HD018184] Funding Source: Medline
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Coreceptor expression is tightly regulated during thymocyte development. Deletion of specific Cd8 enhancers leads to variegated expression of CD8 alpha beta 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.
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