PMID- 9558407
OWN - NLM
STAT- MEDLINE
DCOM- 19980521
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 91
IP  - 9
DP  - 1998 May 1
TI  - Mouse hypoxia-inducible factor-1alpha is encoded by two different mRNA isoforms: 
      expression from a tissue-specific and a housekeeping-type promoter.
PG  - 3471-80
AB  - Hypoxic induction of erythropoietin (Epo) and other oxygen-dependent genes is 
      mediated by the hypoxia-inducible factor-1 (HIF-1), a heterodimeric 
      transactivator consisting of an alpha and a beta subunit. We previously found 
      that the mouse gene encoding HIF-1alpha harbors two alternative first exons (I.1 
      and I.2), giving rise to two different HIF-1alpha mRNA isoforms. Here, we show by 
      RNase protection analysis that the exon I.1-derived mRNA isoform is 
      differentially expressed in mouse tissues, being highest in kidney, tongue, 
      stomach, and testis, but undetectable in liver, whereas the exon I.2 mRNA isoform 
      is ubiquitously expressed. Sequence and methylation analysis showed that, in 
      contrast to exon I.1, exon I.2 resides within a region showing typical features 
      of a CpG island, known to be associated with the 5' end of housekeeping genes. We 
      identified a 232-bp minimal exon I.2 promoter that strongly induced reporter gene 
      expression in mouse L929 fibroblasts and Hepa1 hepatoma cells. In contrast to 
      L929 cells, the exon I.1 promoter was inactive in Hepa1 cells and hypoxic 
      exposure (1% O2) markedly reduced exon I.2 promoter activity in Hepa1 cells. 
      Prolonged exposure of mice to hypoxia (7.5% O2 for up to 72 hours) also caused a 
      decrease in liver HIF-1alpha mRNA, whereas aldolase mRNA levels increased. These 
      findings might be related to the relatively low Epo levels in the adult liver.
FAU - Wenger, R H
AU  - Wenger RH
AD  - Institute of Physiology, University of Zurich-Irchel, Zurich, Switzerland.
FAU - Rolfs, A
AU  - Rolfs A
FAU - Spielmann, P
AU  - Spielmann P
FAU - Zimmermann, D R
AU  - Zimmermann DR
FAU - Gassmann, M
AU  - Gassmann M
LA  - eng
SI  - GENBANK/Y13656
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
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 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Base Sequence
MH  - DNA Methylation
MH  - DNA-Binding Proteins/*genetics
MH  - Exons
MH  - Gene Expression Regulation
MH  - Hypoxia/*genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*genetics
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Tissue Distribution
MH  - Transcription Factors/genetics
EDAT- 1998/05/23 00:00
MHDA- 1998/05/23 00:01
CRDT- 1998/05/23 00:00
PHST- 1998/05/23 00:00 [pubmed]
PHST- 1998/05/23 00:01 [medline]
PHST- 1998/05/23 00:00 [entrez]
AID - S0006-4971(20)55258-0 [pii]
PST - ppublish
SO  - Blood. 1998 May 1;91(9):3471-80.