Histone deacetylase 1 contributes to cell cycle and apoptosis.
Histone deacetylases (HDACs) are generally thought to play important roles in human disease. However, little information is available concerning the specific functions of individual HDACs. We previously reported on transgenic mice that expressed human HDAC1 and experienced steatosis and nuclear pleomorphism in their hepatic tissues. To find out if the over-expression of HDAC1 contributes to the expression of genes related to the cell cycle, apoptosis, and lipid metabolism that eventually contribute to the pathological changes in the livers of the transgenic mice, the expression profiles of the related genes in liver tissues were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The activated human HDAC1 significantly induced the expression levels of mRNA for p53, PPAR-gamma and Bak and reduced the p21 expression level compared with the levels in control littermates. However, the protein levels of p53 and PPAR-gamma were significantly decreased. In conclusion, our results indicate that HDAC1 can regulate gene expression at the mRNA and protein levels independently and that this may be a potential cytopathic factor for hepatic tissue in transgenic mice that over-express HDAC1.
Wang
Ai-Guo
AG
Laboratory of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB); Daejeon 305-806, Korea.
Kim
Sun-Uk
SU
Lee
Sang Ho
SH
Kim
Sang-Keun
SK
Seo
Sang-Beom
SB
Yu
Dae-Yeul
DY
Lee
Dong-Seok
DS
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D047492:Peroxisome Proliferator-Activated Receptors; D016159:Tumor Suppressor Protein p53; D006655:Histone Deacetylases