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

Immunity. 2003 May;18(5):687-98. doi: 10.1016/s1074-7613(03)00109-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Apoptosis / immunology*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / immunology
  • Histone Deacetylases / immunology
  • Histone Deacetylases / metabolism*
  • Humans
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Signal Transduction / immunology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / immunology
  • Transcription Factors / metabolism
  • Transcription, Genetic / immunology*


  • DNA-Binding Proteins
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2D protein, human
  • Myogenic Regulatory Factors
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Antigen, T-Cell
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • HDAC7 protein, human
  • Histone Deacetylases