PMID- 9748288
OWN - NLM
STAT- MEDLINE
DCOM- 19981112
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 40
DP  - 1998 Oct 2
TI  - Hypoxia regulates beta-enolase and pyruvate kinase-M promoters by modulating 
      Sp1/Sp3 binding to a conserved GC element.
PG  - 26087-93
AB  - The transcription rates of glycolytic enzyme genes are coordinately induced when 
      cells are exposed to low oxygen tension. This effect has been described in many 
      cell types and is not restricted to species or phyla. In mammalian cells, there 
      are 11 distinct glycolytic enzymes, at least 9 of which are induced by hypoxia. 
      Recent reports described a role for the hypoxia-inducible factor-1 (HIF-1) in the 
      transcriptional activation of lactate dehydrogenase A, aldolase-A, 
      phosphoglycerate kinase, and enolase-1 genes. It is not known whether the HIF-1 
      factor acts exclusively to regulate these genes during hypoxia, or how the other 
      genes of the pathway are regulated. In this paper, we describe analyses of the 
      muscle-specific pyruvate kinase-M and beta-enolase promoters that implicate 
      additional mechanisms for the regulation of glycolytic enzyme gene transcription 
      by hypoxia. Transient transcription of a reporter gene directed by either 
      promoter was activated when transfected muscle cells were exposed to hypoxia. 
      Neither of these promoters contain HIF-1 binding sites. Instead, the hypoxia 
      response was localized to a conserved GC-rich element positioned immediately 
      upstream of a GATAA site in the proximal promoter regions of both genes. The GC 
      element was essential for both basal and hypoxia-induced expression and bound the 
      transcription factors Sp1 and Sp3. Hypoxia caused the progressive depletion of 
      Sp3 determined by DNA binding studies and Western analyses, whereas Sp1 protein 
      levels remained unchanged. Overexpression of Sp3 repressed expression of 
      beta-enolase promoters. It is concluded that hypoxia activates these glycolytic 
      enzyme gene promoters by down-regulating Sp3, thereby removing the associated 
      transcriptional repression.
FAU - Discher, D J
AU  - Discher DJ
AD  - Department of Molecular and Cellular Pharmacology, University of Miami Medical 
      Center, Miami, Florida 33136, USA.
FAU - Bishopric, N H
AU  - Bishopric NH
FAU - Wu, X
AU  - Wu X
FAU - Peterson, C A
AU  - Peterson CA
FAU - Webster, K A
AU  - Webster KA
LA  - eng
GR  - HL44578/HL/NHLBI NIH HHS/United States
GR  - HL49891/HL/NHLBI 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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Transcription Factors)
RN  - 148710-94-5 (Sp3 Transcription Factor)
RN  - EC 2.7.1.40 (Pyruvate Kinase)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Cells, Cultured
MH  - Conserved Sequence/*genetics
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Down-Regulation/physiology
MH  - Gene Expression Regulation/*genetics
MH  - Genes, Reporter/genetics
MH  - Glycolysis/*physiology
MH  - Hypoxia/*physiopathology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Molecular Sequence Data
MH  - Muscles/enzymology
MH  - Nuclear Proteins/analysis/genetics
MH  - Phosphopyruvate Hydratase/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Pyruvate Kinase/*genetics
MH  - Repressor Proteins/metabolism
MH  - Sp1 Transcription Factor/*metabolism
MH  - Sp3 Transcription Factor
MH  - Transcription Factors/genetics/metabolism
MH  - Transfection/genetics
EDAT- 1998/09/25 00:00
MHDA- 1998/09/25 00:01
CRDT- 1998/09/25 00:00
PHST- 1998/09/25 00:00 [pubmed]
PHST- 1998/09/25 00:01 [medline]
PHST- 1998/09/25 00:00 [entrez]
AID - S0021-9258(19)59926-4 [pii]
AID - 10.1074/jbc.273.40.26087 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Oct 2;273(40):26087-93. doi: 10.1074/jbc.273.40.26087.