[en] We report that HDAC7, a class II histone deacetylase, is highly expressed in CD4(+)CD8(+) double-positive thymocytes. HDAC7 inhibits the expression of Nur77, an orphan receptor involved in apoptosis and negative selection, via the transcription factor MEF2D. HDAC7 is exported from the nucleus during T cell receptor activation, leading to Nur77 expression. A triple HDAC7 mutant (S155A, S318A, S448A) is not exported from the nucleus in response to TCR activation and suppresses TCR-mediated apoptosis. Conversely, a fusion of HDAC7 to the transcriptional activator VP16 activates Nur77 expression. Inhibition of HDAC7 expression by RNA interference causes increased apoptosis in response to TCR activation. These observations define HDAC7 as a regulator of Nur77 and apoptosis in developing thymocytes.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Dequiedt, Franck ; Université de Liège - ULiège > Gembloux Agro Bio-Tech et GIGA-Research
Kasler, Herbert
Fischle, Wolfgang
Kiermer, Veronique
Weinstein, Marc
Herndier, Brian G
Verdin, Eric
Language :
English
Title :
HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis.
Publication date :
2003
Journal title :
Immunity
ISSN :
1074-7613
eISSN :
1097-4180
Publisher :
Cell Press, Cambridge, United States - Massachusetts
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