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
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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Articles in the same Issue
- The arylhydrocarbon receptor: more than a tox story
- The aryl hydrocarbon receptor and light
- The impact of aryl hydrocarbon receptor signaling on matrix metabolism: implications for development and disease
- A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis
- Evidence supporting the hypothesis that one of the main functions of the aryl hydrocarbon receptor is mediation of cell stress responses
- The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function
- Impact of the arylhydrocarbon receptor on eugenol- and isoeugenol-induced cell cycle arrest in human immortalized keratinocytes (HaCaT)
- Aryl hydrocarbon receptor agonists directly activate estrogen receptor α in MCF-7 breast cancer cells
- Identifying target genes of the aryl hydrocarbon receptor nuclear translocator (Arnt) using DNA microarray analysis
- Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice
- 14-3-3 proteins in membrane protein transport
- 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 solution structure of the membrane-proximal cytokine receptor domain of the human interleukin-6 receptor
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