Differential expression of human histone deacetylase mRNAs in response to immune cell apoptosis induction by trichostatin A and butyrate

Biochem Biophys Res Commun. 1998 Jun 29;247(3):833-7. doi: 10.1006/bbrc.1998.8891.


The reversible acetylation of histones by histone deacetylases (HDACs) and acetyltransferases (HATs) plays a fundamental role in gene transcription. We previously showed that HDAC mRNA is upregulated in immune cells upon PHA-induced activation. Little is known, however, about the differential regulation of HDAC mRNAs by the HDAC inhibitors Trichostatin A (TSA) and butyrate, agents known to block proliferation and induce apoptosis. We report that apoptosis-inducing concentrations of TSA and butyrate upregulate the expression of HDAC mRNAs in a differential manner and act synergistically with PHA to induce HDAC expression, suggesting the presence of independent HDAC regulatory mechanisms. Moreover, we show that HDAC inhibitor-induced apoptosis is associated with early abrogation of gamma-IFN production by Th1 lymphocytes and with p53 mRNA downregulation. Our findings highlight the dynamic interplay of cell cycle-, activation- and apoptosis-related proteins in association with time-dependent expression of HDACs and are suggestive of different specific roles for these enzymes.

Publication types

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

MeSH terms

  • Acetyltransferases / physiology
  • Apoptosis / drug effects
  • Butyrates / pharmacology*
  • Butyric Acid
  • CD4-Positive T-Lymphocytes / enzymology*
  • Cell Cycle / physiology
  • Cell Division / drug effects
  • Down-Regulation / drug effects
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Genes, p53 / genetics
  • Histone Acetyltransferases
  • Histone Deacetylases / genetics*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Interferon-gamma / metabolism
  • Isoenzymes / metabolism
  • Phytohemagglutinins / pharmacology
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Thymidine / metabolism
  • Up-Regulation / drug effects


  • Butyrates
  • Hydroxamic Acids
  • Isoenzymes
  • Phytohemagglutinins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Butyric Acid
  • trichostatin A
  • Interferon-gamma
  • Acetyltransferases
  • Histone Acetyltransferases
  • Histone Deacetylases
  • Thymidine