An E-box motif residing in the exon/intron 1 junction regulates both transcriptional activation and splicing of the human norepinephrine transporter gene

The Journal of Biological Chemistry
C H KimK S Kim

Abstract

The norepinephrine transporter (NET) is responsible for the rapid NaCl-dependent uptake of norepinephrine into presynaptic noradrenergic nerve endings. Recently, we have characterized the structural organization of the 5' upstream promoter region of the human NET (hNET) gene. A new intron of 476 base pairs was found in the middle of the 5'-untranslated leader sequence and was shown to robustly enhance the promoter activity. Here, we show that the first hNET intron enhances both the homologous hNET and the heterologous thymidine kinase promoter activities in an orientation- and position-dependent manner. The first hNET intron exhibited a similar promoter-enhancing effect in both SK-N-BE(2)C (NET-positive) and HeLa (NET-negative) cell lines, showing that its function is not cell-specific. Transient transfection assays of a series of deletional constructs show that the first hNET intron contains subdomains with either positive or negative regulatory functions. Furthermore, DNase I footprinting analysis demonstrated that the 5' side of the intron, encompassing the splice donor site, is prominently protected by nuclear proteins isolated from both SK-N-BE(2)C and HeLa cells. The protected nucleotide sequence contains a consensus E-bo...Continue Reading

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Citations

May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Naoe HarafujiMichael Levine
Aug 18, 2009·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Yoosook JoungKwang-Soo Kim
Jan 3, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Chi-Yung ShangSusan Shur-Fen Gau
Apr 4, 2009·Physiological Reviews·Richard KvetnanskyMiklos Palkovits
Jul 26, 2012·Alcoholism, Clinical and Experimental Research·Kate FreemanJames S Schwaber

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