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

被引：84

作者：

Bilic, I

Koesters, C

Unger, B

Sekimata, M

Hertweck, A

Maschek, R

Wilson, CB

Ellmeier, W ^{[1
]}

机构：

[1] Med Univ Vienna, Inst Immunol, A-1090 Vienna, Austria

[2] K Plus Competence Ctr Biomol Therapeut, A-1090 Vienna, Austria

[3] Univ Washington, Dept Immunol, Seattle, WA 98195 USA

来源：

NATURE IMMUNOLOGY | 2006年 / 7卷 / 04期

基金：

奥地利科学基金会;

关键词：

D O I：

10.1038/ni1311

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：392 / 400

页数：9

共 40 条

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