PMID- 10810390
OWN - NLM
STAT- MEDLINE
DCOM- 20000601
LR  - 20191210
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 20
IP  - 2A
DP  - 2000 Mar-Apr
TI  - Promoter specific sensitivity to inhibition of histone deacetylases: implications 
      for hormonal gene control, cellular differentiation and cancer.
PG  - 1017-22
AB  - Alterations in histone acetylation status appear to play a central role in the 
      regulation of neoplasia, tumor suppression, cell cycle control, hormone 
      responsiveness and senescence. These alterations of chromatin control gene 
      transcription. The histone acetylation status is regulated by the equilibrium of 
      histone acetyl-transferase activity (HAT) and the histone deacetylase activity 
      (HDAC). Commonly, DNA-transfection assays are used to measure the effect of 
      histone acetylation and deacetylation on gene transcription. Here we have 
      analyzed the response of various viral long terminal repeats and vertebrate 
      promoters to the specific histone deacetylase inhibitor trichostatin A (TSA). We 
      show that the activity of many, but not all, promoters is increased upon TSA 
      treatment. Interestingly, the lysozyme promoter exhibited TSA resistance, while 
      the activity of metallothionine, the human growth hormone, and the thymidine 
      kinase promoters was increased. Furthermore, we found that all tested viral 
      promoters are induced by TSA. Analysis of the transcriptional behaviour of the 
      thyroid hormone receptor (TR), the cellular homologue of the v-erbA oncogene, 
      revealed that TSA reduced the gene silencing function but had no influence on the 
      hormone-induced gene activation function of the receptor. These results on gene 
      specific effects, together with the HDAC structural data (1), may be a basis for 
      the development of HDAC inhibitors as antitumor agents.
FAU - Dressel, U
AU  - Dressel U
AD  - Genetic Institute, Justus-Liebig-University, Giessen, Germany.
FAU - Renkawitz, R
AU  - Renkawitz R
FAU - Baniahmad, A
AU  - Baniahmad A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Proteins)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 9004-22-2 (Globins)
RN  - 9038-94-2 (Metallothionein)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Line
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Chlorocebus aethiops
MH  - Enzyme Inhibitors/*pharmacology
MH  - *Gene Expression Regulation, Enzymologic/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - Globins/genetics
MH  - *Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/*genetics
MH  - Humans
MH  - Hydroxamic Acids/*pharmacology
MH  - Kidney
MH  - Luciferases/genetics
MH  - Metallothionein/genetics
MH  - *Promoter Regions, Genetic
MH  - Receptors, Thyroid Hormone/*genetics
MH  - Recombinant Proteins/biosynthesis
MH  - Thymidine Kinase/genetics
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 2000/05/16 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/05/16 09:00
PHST- 2000/05/16 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/05/16 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2000 Mar-Apr;20(2A):1017-22.