PMID- 9525945
OWN - NLM
STAT- MEDLINE
DCOM- 19980507
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 14
DP  - 1998 Apr 3
TI  - Selection and analysis of a mutant cell line defective in the hypoxia-inducible 
      factor-1 alpha-subunit (HIF-1alpha). Characterization of hif-1alpha-dependent and 
      -independent hypoxia-inducible gene expression.
PG  - 8360-8
AB  - Hypoxia-inducible expression has been demonstrated for many groups of mammalian 
      genes, and studies of transcriptional control have revealed the existence of 
      hypoxia-responsive elements (HREs) in the cis-acting sequences of several of 
      these genes. These sequences generally contain one or more binding sites for a 
      heterodimeric DNA binding complex termed hypoxia-inducible factor-1 (HIF-1). To 
      analyze this response further, Chinese hamster ovary cells were stably 
      transfected with plasmids bearing HREs linked to genes encoding immunoselectable 
      cell surface markers, and clones that showed reduced or absent hypoxia-inducible 
      marker expression were selected from a mutagenized culture of cells. Analysis of 
      these cells revealed several clones with transacting defects in HRE activation, 
      and in one the defect was identified as a failure to express the alpha-subunit of 
      HIF-1. Comparison of hypoxia-inducible gene expression in wild type, 
      HIF-1alpha-defective, and HIF-1alpha-complemented cells revealed two types of 
      response. For some genes (e.g. glucose transporter-1), hypoxia-inducible 
      expression was critically dependent on HIF-1alpha, whereas for other genes (e.g. 
      heme oxygenase-1) hypoxia-inducible expression appeared largely independent of 
      the expression of HIF-1alpha. These experiments show the utility of mutagenesis 
      and selection of mutant cells in the analysis of mammalian transcriptional 
      responses to hypoxia and demonstrate the operation of HIF-1alpha-dependent and 
      HIF-1alpha-independent pathways of hypoxia-inducible gene expression in Chinese 
      hamster ovary cells.
FAU - Wood, S M
AU  - Wood SM
AD  - Erythropoietin Group, Institute of Molecular Medicine, John Radcliffe Hospital, 
      Oxford OX3 9DS, United Kingdom.
FAU - Wiesener, M S
AU  - Wiesener MS
FAU - Yeates, K M
AU  - Yeates KM
FAU - Okada, N
AU  - Okada N
FAU - Pugh, C W
AU  - Pugh CW
FAU - Maxwell, P H
AU  - Maxwell PH
FAU - Ratcliffe, P J
AU  - Ratcliffe PJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
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 (DNA-Binding Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - *CHO Cells
MH  - Cell Hypoxia/*genetics
MH  - Cricetinae
MH  - DNA-Binding Proteins/*genetics
MH  - *Gene Expression Regulation
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - *Mutation
MH  - Nuclear Proteins/*genetics
MH  - *Transcription Factors
EDAT- 1998/05/09 00:00
MHDA- 1998/05/09 00:01
CRDT- 1998/05/09 00:00
PHST- 1998/05/09 00:00 [pubmed]
PHST- 1998/05/09 00:01 [medline]
PHST- 1998/05/09 00:00 [entrez]
AID - S0021-9258(18)52566-7 [pii]
AID - 10.1074/jbc.273.14.8360 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Apr 3;273(14):8360-8. doi: 10.1074/jbc.273.14.8360.