Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells

Biochem Biophys Res Commun. 1998 Jan 26;242(3):648-52. doi: 10.1006/bbrc.1997.8033.


The nucleosomal histones can be modified through reversible acetylation by histone acetyltransferases (HATs) and deacetylases (HDACs). HATs induce nucleosomal relaxation and allow DNA-binding by transcriptional activators. HDACs from corepressor complexes which negatively regulate cell growth. However, the HDAC inhibitors butyrate and Trichostatin A block T cell proliferation, suggesting that not all effects of HDACs lead to repression. Using mRNA differential display and 5'RACE we isolated human HDAC3, a novel gene that is upregulated in PHA-activated T cell clones. HDAC3 is homologous to other human HDACs and yeast RPD3. In peripheral blood mononuclear cells (PBMCs), activation by PHA, PMA and alpha-CD3 increased HDAC mRNA but no effect was seen with IFN-gamma, LPS, or IL-4. In contrast, GMCSF downregulated PBMC levels of HDAC3 mRNA. All HDACs were found to be ubiquitously expressed in immune and non-immune tissues. In human myeloid leukemia THP-1 cells, HDAC3 transfection resulted in increased size, aberrant nuclear morphology and cell cycle G2/M cell accumulation. Functional activity of the expressed HDAC3 protein was confirmed in alpha-HDAC3 antibody immunoprecipitates by a histone deacetylase assay. Our study suggests the participation of HDACs in cell cycle progression and activation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Blotting, Northern
  • CD3 Complex
  • Cell Cycle / physiology
  • Cloning, Molecular
  • DNA / analysis
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Phytohemagglutinins / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Sequence Alignment
  • Sequence Analysis, DNA
  • T-Lymphocytes / enzymology*
  • Transfection / genetics
  • Tumor Cells, Cultured


  • CD3 Complex
  • Phytohemagglutinins
  • RNA, Messenger
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA
  • Histone Deacetylases
  • histone deacetylase 3

Associated data

  • GENBANK/AF053137
  • GENBANK/AF053138
  • GENBANK/AF053139
  • GENBANK/U66914