Cross-talk between hypoxic and circadian pathways: cooperative roles for hypoxia-inducible factor 1α and CLOCK in transcriptional activation of the vasopressin gene

The vasopressin gene is expressed in the suprachiasmatic nucleus where the basic helix-loop-helix (bHLH)-PAS factors CLOCK and MOP3 regulate circadian expression through interactions with E-box sequences. We have examined vasopressin gene regulation by HIF-1alpha, a bHLH-PAS factor involved in responses to hypoxia. By transfecting Neuro-2A cells with 5' flanking regions of vasopressin gene driving a luciferase reporter, we have shown that CLOCK and HIF-1alpha cooperate in the induction of expression from 1000 bp and 350 bp of the vasopressin promoter but do not activate a 120-bp promoter fragment. The region between -191 and -128 contains an E-box A that appears to be essential for HIF-1alpha/CLOCK-mediated transcriptional activity. However, gel-shift analysis shows that the cooperative effect of HIF-1alpha and CLOCK results in MOP3 binding, but does not involve heterodimerization of HIF-1alpha/CLOCK, at E-box A. These data indicate that cross-talk between mediators of hypoxic and circadian pathways can regulate target genes.

[1]  M. Ikeda,et al.  cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage. , 1997, Biochemical and biophysical research communications.

[2]  O. Gotoh,et al.  cDNA Cloning and Tissue-Specific Expression of a Novel Basic Helix-Loop-Helix/PAS Factor (Arnt2) with Close Sequence Similarity to the Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) , 1996 .

[3]  Y. Loh,et al.  The Neuro-2a neuroblastoma cell line expresses [Met]-enkephalin and vasopressin mRNA and peptide , 1995, Molecular and Cellular Endocrinology.

[4]  Minoru Tanaka,et al.  Positional Cloning of the Mouse Circadian Clock Gene , 1997, Cell.

[5]  S. McKnight,et al.  Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. , 1997, Genes & development.

[6]  David Baunoch,et al.  Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT , 1997, Nature.

[7]  G. Semenza,et al.  Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Rubenstein,et al.  Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome , 1996, Molecular and Cellular Neuroscience.

[9]  O. Gotoh,et al.  cDNA cloning of a murine homologue of Drosophila single-minded, its mRNA expression in mouse development, and chromosome localization. , 1996, Biochemical and biophysical research communications.

[10]  M. Simon,et al.  The bHLH/PAS factor MOP3 does not participate in hypoxia responses. , 2002, Biochemical and biophysical research communications.

[11]  S. Crews,et al.  Control of Cell Lineage-specific Development and Transcription by Bhlh–pas Proteins , 2022 .

[12]  D. Carter,et al.  Nuclear mechanisms mediate rhythmic changes in vasopressin mRNA expression in the rat suprachiasmatic nucleus. , 1992, Brain research. Molecular brain research.

[13]  M. Gassmann,et al.  Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  S. Yoon,et al.  Tissue-specific transcription of the rat tyrosine hydroxylase gene requires synergy between an AP-1 motif and an overlapping E box-containing dyad , 1992, Neuron.

[15]  O. Hankinson,et al.  Cloning of a factor required for activity of the Ah (dioxin) receptor. , 1991, Science.

[16]  J. Coulson Chapter 26 Positive and negative regulators of the vasopressin gene promoter in small cell lung cancer , 2002 .

[17]  J. Hogenesch,et al.  Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway* , 1997, The Journal of Biological Chemistry.

[18]  J. Takahashi,et al.  The Basic Helix-Loop-Helix-PAS Protein MOP9 Is a Brain-Specific Heterodimeric Partner of Circadian and Hypoxia Factors , 2000, The Journal of Neuroscience.

[19]  Cheryl Wolting,et al.  Cloning and chromosomal localization of a new member of the bHLH/PAS transcription factor family , 1998, Mammalian Genome.

[20]  Y Fujii-Kuriyama,et al.  A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Hogenesch,et al.  The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Gainer,et al.  Gene regulation in the magnocellular hypothalamo-neurohypophysial system. , 2001, Physiological reviews.

[23]  Moore Ry Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. , 1983 .

[24]  D. P. King,et al.  Role of the CLOCK protein in the mammalian circadian mechanism. , 1998, Science.

[25]  Mark J. Zylka,et al.  A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock , 1999, Cell.

[26]  Andrew S. Burrell,et al.  Alterations of AP-1 and CREB protein DNA binding in rat supraoptic and paraventricular nuclei by acute and repeated hyperosmotic stress , 2001, Brain Research Bulletin.

[27]  Saroj P. Mathupala,et al.  Glucose Catabolism in Cancer Cells , 2001, The Journal of Biological Chemistry.

[28]  G. Semenza,et al.  The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. , 1998, Genomics.

[29]  C. Bradfield,et al.  Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Quinn,et al.  Characterization of potential regulatory elements within the rat arginine vasopressin proximal promoter , 1999, Neuropeptides.