HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis

Franck Dequiedt; Herbert Kasler; Wolfgang Fischle; Veronique Kiermer; Marc Weinstein; Brian G. Herndier; Eric Verdin

doi:10.1016/S1074-7613(03)00109-2

HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis

Franck Dequiedt, Herbert Kasler, Wolfgang Fischle, Veronique Kiermer, Marc Weinstein, Brian G. Herndier, Eric Verdin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

193 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	687-698
Number of pages	12
Journal	Immunity
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/S1074-7613(03)00109-2
State	Published - May 1 2003
Externally published	Yes

Bibliographical note

Funding Information:
We thank John C.W. Carroll and Stephen Gonzales for graphics, Heather Gravois for manuscript preparation, Stephen Ordway and Gary Howard for editorial assistance, and Astar Winoto and Didier Trono for reagents. We thank Kavhe Bastani and Mike McCune for discussions, Christophe Kreiss for help with TaqMan analysis, and Jason Barber for statistical analysis. This work was supported in part by NIH grant GM51671 and by institutional funds from the Gladstone Institute of Virology and Immunology (E.V.). F.D. is a research associate from the Belgian National Fund of Scientific Research and was supported in part by a fellowship from the International Agency for Research on Cancer. W.F. was supported in part by a fellowship from the Boehringer Ingelheim Foundation, Germany.

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S1074-7613(03)00109-2

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title = "HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis",

abstract = "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.",

author = "Franck Dequiedt and Herbert Kasler and Wolfgang Fischle and Veronique Kiermer and Marc Weinstein and Herndier, {Brian G.} and Eric Verdin",

note = "Funding Information: We thank John C.W. Carroll and Stephen Gonzales for graphics, Heather Gravois for manuscript preparation, Stephen Ordway and Gary Howard for editorial assistance, and Astar Winoto and Didier Trono for reagents. We thank Kavhe Bastani and Mike McCune for discussions, Christophe Kreiss for help with TaqMan analysis, and Jason Barber for statistical analysis. This work was supported in part by NIH grant GM51671 and by institutional funds from the Gladstone Institute of Virology and Immunology (E.V.). F.D. is a research associate from the Belgian National Fund of Scientific Research and was supported in part by a fellowship from the International Agency for Research on Cancer. W.F. was supported in part by a fellowship from the Boehringer Ingelheim Foundation, Germany.",

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AU - Fischle, Wolfgang

AU - Kiermer, Veronique

AU - Weinstein, Marc

AU - Herndier, Brian G.

AU - Verdin, Eric

N1 - Funding Information: We thank John C.W. Carroll and Stephen Gonzales for graphics, Heather Gravois for manuscript preparation, Stephen Ordway and Gary Howard for editorial assistance, and Astar Winoto and Didier Trono for reagents. We thank Kavhe Bastani and Mike McCune for discussions, Christophe Kreiss for help with TaqMan analysis, and Jason Barber for statistical analysis. This work was supported in part by NIH grant GM51671 and by institutional funds from the Gladstone Institute of Virology and Immunology (E.V.). F.D. is a research associate from the Belgian National Fund of Scientific Research and was supported in part by a fellowship from the International Agency for Research on Cancer. W.F. was supported in part by a fellowship from the Boehringer Ingelheim Foundation, Germany.

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N2 - 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.

AB - 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.

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HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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