PMID- 9654078
OWN - NLM
STAT- MEDLINE
DCOM- 19980729
LR  - 20191210
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 253
IP  - 3
DP  - 1998 May 1
TI  - Oxygen-regulated erythropoietin gene expression is dependent on a CpG 
      methylation-free hypoxia-inducible factor-1 DNA-binding site.
PG  - 771-7
AB  - The hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in 
      the expression of oxygen-regulated genes such as that for erythropoietin. 
      Following exposure to low oxygen partial pressure (hypoxia), HIF-1 binds to an 
      hypoxia-response element located 3' to the erythropoietin gene and confers 
      activation of erythropoietin expression. The conserved core HIF-1 binding site 
      (HBS) of the erythropoietin 3' enhancer (CGTG) contains a CpG dinucleotide known 
      to be a potential target of cytosine methylation. We found that methylation of 
      the HBS abolishes HIF-1 DNA binding as well as hypoxic reporter gene activation, 
      suggesting that a methylation-free HBS is mandatory for HIF-1 function. The in 
      vivo methylation pattern of the erythropoietin 3' HBS in various human cell lines 
      and mouse organs was assessed by genomic Southern blotting using a 
      methylation-sensitive restriction enzyme. Whereas this site was essentially 
      methylation-free in the erythropoietin-producing cell line Hep3B, a direct 
      correlation between erythropoietin protein expression and the degree of 
      erythropoietin 3' HBS methylation was found in different HepG2 sublines. However, 
      the finding that this site is partially methylation-free in human cell lines and 
      mouse tissues that do not express erythropoietin suggests that there might be a 
      general selective pressure to keep this site methylation-free, independent of 
      erythropoietin expression.
FAU - Wenger, R H
AU  - Wenger RH
AD  - Institute of Physiology, University of Zurich-Irchel, Zurich, Switzerland. 
      labbauer@physiol.unizh.ch
FAU - Kvietikova, I
AU  - Kvietikova I
FAU - Rolfs, A
AU  - Rolfs A
FAU - Camenisch, G
AU  - Camenisch G
FAU - Gassmann, M
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 11096-26-7 (Erythropoietin)
RN  - 2382-65-2 (cytidylyl-3'-5'-guanosine)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Carcinoma, Hepatocellular
MH  - *Cell Hypoxia
MH  - Cell Nucleus/metabolism
MH  - DNA Methylation
MH  - DNA-Binding Proteins/*metabolism
MH  - Dinucleoside Phosphates/*metabolism
MH  - Erythropoietin/*biosynthesis
MH  - *Gene Expression Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kidney/embryology/growth & development/metabolism
MH  - L Cells
MH  - Leukemia
MH  - Liver/embryology/growth & development/metabolism
MH  - Liver Neoplasms
MH  - Luciferases/biosynthesis
MH  - Mice
MH  - Neuroblastoma
MH  - Nuclear Proteins/*metabolism
MH  - Organ Specificity
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Transcription Factors/metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1998/07/08 00:00
MHDA- 1998/07/08 00:01
CRDT- 1998/07/08 00:00
PHST- 1998/07/08 00:00 [pubmed]
PHST- 1998/07/08 00:01 [medline]
PHST- 1998/07/08 00:00 [entrez]
AID - 10.1046/j.1432-1327.1998.2530771.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1998 May 1;253(3):771-7. doi: 10.1046/j.1432-1327.1998.2530771.x.