PMID- 10607478
OWN - NLM
STAT- MEDLINE
DCOM- 20000301
LR  - 20131121
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 68
IP  - 4
DP  - 1999 Dec
TI  - Characterization of the human very-long-chain acyl-CoA dehydrogenase gene 
      promoter region: a role for activator protein 2.
PG  - 481-7
AB  - Very-long-chain acyl-CoA dehydrogenase (VLCAD) is one of a family of 
      nuclear-encoded enzymes that catalyze the initial step in mitochondrial fatty 
      acid beta-oxidation (FAO). Previous studies have indicated that two other members 
      of the AD gene family (medium-chain AD and long-chain AD) are controlled at the 
      transcriptional level by nuclear hormone receptors. In this study, we have cloned 
      and characterized the human VLCAD gene promoter region to identify cis-acting 
      elements involved in its transcriptional control. VLCAD gene promoter-luciferase 
      reporter (VLCAD-Luc) constructs were found to be transcriptionally active in a 
      variety of mammalian cell lines and in primary rat cardiomyocytes when driven by 
      varying lengths of the VLCAD promoter region. Removal of a 20-bp DNA segment of 
      the proximal VLCAD gene promoter markedly reduced the transcriptional activity of 
      VLCAD-Luc constructs. Gel mobility shift assays identified a DNA-binding activity 
      in nuclear extracts prepared from human hepatoma G2 cells that interacted with 
      the 20-bp regulatory region. Competition studies revealed that this DNA-binding 
      activity could be abolished by a molar excess of unlabeled specific 
      oligonucleotide as well as a DNA fragment containing an activator protein 2 
      (AP-2)-binding site but not by an unrelated nonspecific DNA fragment. These 
      results provide an initial characterization of the human VLCAD gene promoter, 
      identify AP-2 as a candidate activator of VLCAD gene transcription, and suggest 
      that VLCAD gene transcription may be regulated by pathways distinct from that of 
      other AD genes.
CI  - Copyright 1999 Academic Press.
FAU - Zhou, Y
AU  - Zhou Y
AD  - Department of Pediatrics, Washington University School of Medicine and St. Louis 
      Children's Hospital, St. Louis, Missouri 63110, USA.
FAU - Kelly, D P
AU  - Kelly DP
FAU - Strauss, A W
AU  - Strauss AW
FAU - Sims, H
AU  - Sims H
FAU - Zhang, Z
AU  - Zhang Z
LA  - eng
GR  - P01-DK33487/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (activator protein-2 binding element)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.3.8.8 (Acyl-CoA Dehydrogenase, Long-Chain)
SB  - IM
MH  - Acyl-CoA Dehydrogenase, Long-Chain/*genetics
MH  - Animals
MH  - Binding, Competitive
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/*genetics
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Luciferases/genetics
MH  - Mitochondria/metabolism
MH  - *Promoter Regions, Genetic
MH  - Rats
MH  - Transcription, Genetic
EDAT- 1999/12/23 09:00
MHDA- 2000/03/04 09:00
CRDT- 1999/12/23 09:00
PHST- 1999/12/23 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/12/23 09:00 [entrez]
AID - S1096-7192(99)92933-5 [pii]
AID - 10.1006/mgme.1999.2933 [doi]
PST - ppublish
SO  - Mol Genet Metab. 1999 Dec;68(4):481-7. doi: 10.1006/mgme.1999.2933.