title: HIF1A gene transcription is dependent on a core promoter sequence encompassing activating and inhibiting sequences located upstream from the transcription initiation site and cis elements located within the 5'UTR.
abstract: Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of two subunits, HIF-1alpha and ARNT, which is activated under hypoxia. HIF-1alpha mRNA is expressed constitutively in a wide variety of cell types, whereas in some others HIF1A gene expression is upregulated by hypoxia. In this report, we show that in endothelial cells (HMEC-1) the HIF-1alpha mRNA expression level is the same in both normoxia and hypoxia. Deletion analysis experiments of the HIF1A promoter showed that in hypoxia HIF1A gene expression is upregulated through a short sequence located next to the transcription initiation site. We also show that in hypoxia another sequence located upstream from the +1 initiation site plays an inhibitory role on HIF1A transcription in HMEC-1 but not in hepatoma cells and brings back this expression level to that observed in normoxia. Finally, we demonstrate that HIF1A gene transcription is dependent on Sp1 binding sites and that the 5'UTR sequence also contains other important cis-acting elements.
authors.affiliation: Laboratoire de Biochimie et Biologie Cellulaire, Facultés Universitaires de la Paix, 61 rue de Bruxelles, Namur, 5000, Belgium. emmanuel.minet@fundp.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Minet
authors.forename: I
authors.initials: I
authors.lastname: Ernest
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: I
authors.initials: I
authors.lastname: Roland
authors.forename: J
authors.initials: J
authors.lastname: Remacle
authors.forename: M
authors.initials: M
authors.lastname: Raes
authors.forename: C
authors.initials: C
authors.lastname: Michiels
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D017931:DNA Primers; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D004247:DNA