PMID- 10788445
OWN - NLM
STAT- MEDLINE
DCOM- 20000601
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 18
DP  - 2000 May 5
TI  - A conserved nuclear receptor consensus sequence (DR-4) mediates transcriptional 
      activation of the chicken CYP2H1 gene by phenobarbital in a hepatoma cell line.
PG  - 13362-9
AB  - Phenobarbital-responsive DNA elements were identified in the 5'-flanking region 
      of the chicken CYP2H1 gene by in reporter gene assays in a chicken hepatoma cell 
      line (leghorn male hepatoma (LMH)). A 264-base pair (bp) enhancer sequence 
      (phenobarbital-responsive unit (PBRU)) responded to phenobarbital and a variety 
      of phenobarbital-type inducers. Analysis of putative transcription factor binding 
      sites within the 264-bp element revealed a nuclear receptor half-site repeat 
      (DR-4) neighboring a putative nuclear factor-1 site. This motif resembles 
      phenobarbital response elements in the flanking regions of three 
      phenobarbital-inducible genes, rat CYP2B2, mouse Cyp2b10, and human CYP2B6. 
      Activation of the 264-bp element was eliminated after site-directed mutagenesis 
      of the DR-4 hexamer half-sites. Evidence for evolutionary conservation of this 
      recognition site was indicated by activation in LMH cells of a mouse Cyp2b10 
      phenobarbital-responsive enhancer by the same spectrum of inducers that activate 
      the CYP2H1 264-bp PBRU. Inhibition of this activation by okadaic acid may explain 
      the reported inhibitory effects on induction of CYP2B1/2 and Cyp2b10 by this 
      phosphatase inhibitor. We show that this inhibition occurs directly on the 264-bp 
      PBRU, whereas the proximal promoter of CYP2H1 is induced by okadaic acid in 
      reporter gene assays. These experiments exploit the unique phenobarbital 
      inducibility of the hepatoma-derived cell line LMH.
FAU - Handschin, C
AU  - Handschin C
AD  - Department of Pharmacology/Neurobiology, Biozentrum of the University of Basel, 
      Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
FAU - Meyer, U A
AU  - Meyer UA
LA  - eng
SI  - GENBANK/AF236668
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Conserved Sequence
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Liver Neoplasms, Experimental/*genetics
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phenobarbital/*pharmacology
MH  - Rats
MH  - Receptors, Cytoplasmic and Nuclear/*genetics
MH  - Sequence Alignment
MH  - Transcriptional Activation/*drug effects
MH  - Tumor Cells, Cultured
EDAT- 2000/05/02 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/05/02 09:00
PHST- 2000/05/02 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/05/02 09:00 [entrez]
AID - S0021-9258(19)80695-6 [pii]
AID - 10.1074/jbc.275.18.13362 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 May 5;275(18):13362-9. doi: 10.1074/jbc.275.18.13362.