Home Life Sciences The K+ channel gene, Kcnb1: genomic structure and characterization of its 5′-regulatory region as part of an overlapping gene group
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The K+ channel gene, Kcnb1: genomic structure and characterization of its 5′-regulatory region as part of an overlapping gene group

  • Karim Roder and Gideon Koren
Published/Copyright: September 14, 2006
Biological Chemistry
From the journal Volume 387 Issue 9

Abstract

Kcnb1 expression is down-regulated in certain types of cardiomyopathy. As a first step towards understanding Kcnb1 regulation, we determined its genomic structure and characterized its 5′-regulatory region. Two species of Kcnb1 mRNA were found to arise from alternative usage of two highly GC-rich promoters (P1, P2). While transcripts arising from P1 were mainly detected in brain, P2 transcripts were highly expressed in heart and brain. Core regulatory regions were characterized for P1 and P2. The mutation of a potential Nur77/Nurr1/NOR-1 binding site, NBREKcnb1, conserved in both human and mouse, resulted in a significant decrease in basal P2 promoter activity. Luciferase activities of the longest promoter-reporter construct reflected the level of endogenous Kcnb1 mRNA in myoblast, smooth muscle, and pituitary cell lines. Hyperosmolarity increased Kcnb1 mRNA concentration two-fold, mainly at the transcriptional level in clonal pituitary cells. These findings provide a basis for future studies of (post)transcriptional mechanism(s) down-regulating Kcnb1 expression in a variety of cardiomyopathies and point towards a possible involvement of Kcnb1 in pituitary cell excitability and secretory activity regulated by osmolarity.

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References

Bock, J.H., Shuck, M.E., Benjamin, C.W., Chee, M., Bienkowski, M.J., and Slightom, J.L. (1997). Nucleotide sequence analysis of the human KCNJ1 potassium channel locus. Gene188, 9–16.10.1016/S0378-1119(96)00759-7Search in Google Scholar

Coma, M., Vicente, R., Busquets, S., Carbo, N., Tamkun, M.M., Lopez-Soriano, F.J., Argiles, J.M., and Felipe, A. (2003). Impaired voltage-gated K+ channel expression in brain during experimental cancer cachexia. FEBS Lett.536, 45–50.10.1016/S0014-5793(03)00009-7Search in Google Scholar

Drewe, J.A., Verma, S., Frech G., and Joho, R.H. (1992). Distinct spatial and temporal expression patterns of K+ channel mRNAs from different subfamilies. J. Neurosci.12, 538–548.10.1523/JNEUROSCI.12-02-00538.1992Search in Google Scholar

Ebihara, M., Ohba, H., Kikuchi, M., and Yoshikawa, T. (2004). Structural characterization and promoter analysis of human potassium channel Kv8.1 (KCNV1) gene. Gene325, 89–96.Search in Google Scholar

Ekhterae, D., Platoshyn, O., Krick, S., Yu, Y., McDaniel, S.S., and Yuan, J.X. (2001). Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. Am. J. Physiol. Cell. Physiol.281, C157–C165.10.1152/ajpcell.2001.281.1.C157Search in Google Scholar

Gan, L., Hahn, S.J., and Kaczmarek, L.K. (1999). Cell type-specific expression of the Kv3.1 gene is mediated by a negative element in the 5′ untranslated region of the Kv3.1 promoter. J. Neurochem.73, 1350–1362.Search in Google Scholar

Huang, B., Qin, D., and El-Sherif, N. (2000). Early down-regulation of K+ channel genes and currents in the postinfarction heart. J. Cardiovasc. Electrophysiol.11, 1252–1261.10.1046/j.1540-8167.2000.01252.xSearch in Google Scholar

Ishizaki, F., Harada, T., Yoshinaga, H., Nakayama, T., Yamamura, Y., and Nakamura, S. (1996). Prolonged QTc intervals in Parkinson's disease – relation to sudden death and autonomic dysfunction. No To Shinkei48, 443–448.Search in Google Scholar

Law, S.W., Conneely, O.M., DeMayo, F.J., and O'Malley, B.W. (1992). Identification of a new brain-specific transcription factor, NURR1. Mol. Endocrinol.6, 2129–2135.Search in Google Scholar

Le, W.D., Xu, P., Jankovic, J., Jiang, H., Appel, S.H., Smith, R.G., and Vassilatis, D.K. (2003). Mutations in NR4A2 associated with familial Parkinson disease. Nat. Genet.33, 85–89.10.1038/ng1066Search in Google Scholar

MacDonald, P.E., Sewing, S., Wang, J., Joseph, J.W., Smukler, S.R., Sakellaropoulos, G., Saleh, M.C., Chan, C.B., Tsushima, R.G., Salapatek, A.M., and Wheeler, M.B. (2002). Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic β-cells enhances glucose-dependent insulin secretion. J. Biol. Chem.277, 44938–44945.Search in Google Scholar

Mangelsdorf, D.J., Thummel, C., Beato, M., Herrlich, P., Schutz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995). The nuclear receptor superfamily: the second decade. Cell83, 835–839.10.1016/0092-8674(95)90199-XSearch in Google Scholar

Mattick, J.S. (2001). Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep.2, 986–991.10.1093/embo-reports/kve230Search in Google Scholar PubMed PubMed Central

Michelhaugh, S.K., Vaitkevicius, H., Wang, J., Bouhamdan, M., Krieg, A.R., Walker, J.L., Mendiratta, V., and Bannon, M.J. (2005). Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity. J. Neurochem.95, 1342–1350.10.1111/j.1471-4159.2005.03458.xSearch in Google Scholar PubMed

Miyata, A., Hara, S., Yokoyama, C., Inoue, H., Ullrich, V., and Tanabe, T. (1994). Molecular cloning and expression of human prostacyclin synthase. Biochem. Biophys. Res. Commun.200, 1728–1734.10.1006/bbrc.1994.1652Search in Google Scholar PubMed

Mori, Y., Folco, E., and Koren, G. (1995). GH3 cell-specific expression of Kv1.5 gene. Regulation by a silencer containing a dinucleotide repetitive element. J. Biol. Chem.270, 27788–27796.Search in Google Scholar

Ohkura, N., Hijikuro, M., Yamamoto, A., and Miki, K. (1994). Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Biochem. Biophys. Res. Commun.205, 1959–1965.10.1006/bbrc.1994.2900Search in Google Scholar

Oka, H., Mochio, S., Sato, H., and Katayama, K. (1997). Prolongation of QTc interval in patients with Parkinson's disease. Eur. Neurol.37, 186–189.10.1159/000117432Search in Google Scholar

Ottschytsch, N., Raes, A., Van Hoorick, D., and Snyders, D.J. (2002). Obligatory heterotetramerization of three previously uncharacterized Kv channel α-subunits identified in the human genome. Proc. Natl. Acad. Sci. USA99, 7986–7991.10.1073/pnas.122617999Search in Google Scholar

Pak, M.D., Covarrubias, M., Ratcliffe, A., and Salkoff, L. (1991). A mouse brain homolog of the Drosophila Shab K+ channel with conserved delayed-rectifier properties. J. Neurosci.11, 869–880.10.1523/JNEUROSCI.11-03-00869.1991Search in Google Scholar

Pal, S., Hartnett, K.A., Nerbonne, J.M., Levitan, E.S., and Aizenman, E. (2003). Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels. J. Neurosci.23, 4798–4802.Search in Google Scholar

Qin, D., Huang, B., Deng, L., El-Adawi, H., Ganguly, K., Sowers, J.R., and El-Sherif, N. (2001). Downregulation of K+ channel genes expression in type I diabetic cardiomyopathy. Biochem. Biophys. Res. Commun.283, 549–553.10.1006/bbrc.2001.4825Search in Google Scholar

Rajpal, A., Cho, Y.A., Yelent, B., Koza-Taylor, P.H., Li, D., Chen, E., Whang, M., Kang, C., Turi, T.G., and Winoto, A. (2003). Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J.22, 6526–6536.10.1093/emboj/cdg620Search in Google Scholar

Salinas, M., Duprat, F., Heurteaux, C., Hugnot, J.P., and Lazdunski, M. (1997). New modulatory α subunits for mammalian Shab K+ channels. J. Biol. Chem.272, 24371–24379.10.1074/jbc.272.39.24371Search in Google Scholar

Saucedo-Cardenas, O., Quintana-Hau, J.D., Le, W.D., Smidt, M.P., Cox, J.J., De Mayo, F., Burbach, J.P., and Conneely, O.M. (1998). Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc. Natl. Acad. Sci. USA95, 4013–4018.10.1073/pnas.95.7.4013Search in Google Scholar

Shabalina, S.A., Ogurtsov, A.Y., Kondrashov, V.A., and Kondrashov, A.S. (2001). Selective constraint in intergenic regions of human and mouse genomes. Trends Genet.17, 373–376.10.1016/S0168-9525(01)02344-7Search in Google Scholar

Vullhorst, D., Jockusch, H., and Bartsch, J.W. (2001). The genomic basis of K(V)3.4 potassium channel mRNA diversity in mice. Gene264, 29–35.Search in Google Scholar

Wilson, T.E., Fahrner, T.J., Johnston, M., and Milbrandt, J. (1991). Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science252, 1296–1300.10.1126/science.1925541Search in Google Scholar PubMed

Wright, F.A., Lemon, W.J., Zhao, W.D., Sears, R., Zhuo, D., Wang, J.P., Yang, H.Y., Baer, T., Stredney, D., Spitzner, J., et al. (2001). A draft annotation and overview of the human genome. Genome Biol. 2, RESEARCH0025.Search in Google Scholar

Published Online: 2006-09-14
Published in Print: 2006-09-01

©2006 by Walter de Gruyter Berlin New York

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