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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

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

Franck Dequiedt1, Herbert Kasler, Wolfgang Fischle

  • 1Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco 94141, USA.

Immunity
|May 20, 2003
PubMed

Insights

Histone deacetylase 7 (HDAC7) regulates thymocyte apoptosis by controlling Nur77 expression. Nuclear export of HDAC7 during T cell receptor activation allows Nur77 expression, promoting apoptosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Histone deacetylases (HDACs) play critical roles in gene regulation.
  • Class II HDACs, including HDAC7, are involved in various cellular processes.
  • Thymocyte development and T cell receptor (TCR) signaling are crucial for adaptive immunity.

Purpose of the Study:

  • To investigate the role of HDAC7 in thymocyte development and apoptosis.
  • To elucidate the mechanism by which HDAC7 regulates Nur77 expression.
  • To determine the impact of HDAC7 activity on TCR-mediated apoptosis.

Main Methods:

  • Quantitative analysis of HDAC7 expression in thymocytes.
  • Investigation of HDAC7's interaction with MEF2D and Nur77.
  • Utilizing site-directed mutagenesis to create non-exportable HDAC7 mutants.
  • Employing RNA interference to inhibit HDAC7 expression.
  • Assessing apoptosis in response to TCR activation.

Main Results:

  • HDAC7 is highly expressed in CD4(+)CD8(+) double-positive thymocytes.
  • HDAC7 inhibits Nur77 expression via MEF2D.
  • TCR activation induces nuclear export of HDAC7, leading to Nur77 expression and apoptosis.
  • A triple mutant of HDAC7, unable to be exported from the nucleus, suppresses TCR-mediated apoptosis.
  • Inhibition of HDAC7 enhances TCR-induced apoptosis.

Conclusions:

  • HDAC7 acts as a key regulator of Nur77 expression and apoptosis during thymocyte development.
  • HDAC7's subcellular localization is critical for controlling TCR-mediated apoptosis.
  • These findings highlight HDAC7 as a potential therapeutic target in T cell-related disorders.

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