Regulation of Nur77 transcription by HDAC7, a thymus-specific histone deacetylase
byDequiedt F., Kasler H., Fischle W., Kiermer V., Weinstein M., Herndier B., Verdin E.
Dequiedt F., Kasler H., Fischle W., Kiermer V., Weinstein M., Herndier B. and Verdin E. (2003) Regulation of Nur77 transcription by HDAC7, a thymus-specific histone deacetylase. Immunity 18:687-698
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 ofHDAC7 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.