Differential expression of class I HDACs: roles of cell density and cell cycle.
Enzymes which affect histone acetylation status have been shown to play an important role in determining transcriptional activity in chromatin through conformational modification of its structure. Since the timely presence of such enzymes may be of critical importance, our experiments were designed to determine whether the level of expression of HDAC1 is cell cycle dependent and/or affected by a high cell density. Our results show that in mouse fibroblasts the expression of mHDAC1 is neither affected by cell cycle phases nor by cell density. In contrast, the expression of several hHDACs including hHDAC1 were affected in a cell density dependent fashion in the human prostate adenocarcinoma cell line PC3, paralleling our previously published findings in the hepatocellular carcinoma derived cell line Hep3B. Differential recruitment of HDAC mRNAs suggests that these enzymes may play unique roles in different cell types and under different environmental conditions (i.e., exposure to various cell densities and cell-cell contacts). Our study has implications for the proposed use of HDAC inhibitors in the treatment of human malignancy, highlighting issues of drug action selectivity in tissues and potential secondary effects.
Dangond
F
F
Laboratory of Transcriptional and Immune Regulation, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Henriksson
M
M
Zardo
G
G
Caiafa
P
P
Ekström
T J
TJ
Gray
S G
SG
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D015342:DNA Probes; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology*
D002087:Butyrates; D015342:DNA Probes; D012259:Ribonuclease, Pancreatic; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases