Structure of the 5'-flanking regulatory region and gene for the human growth factor-activatable Na/H exchanger NHE-1

R. Tyler Miller, Laurent Counillon, Gilles Pages, Richard P. Lifton, Claude Sardet, Jacques Pouysségur

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64 Scopus citations

Abstract

The amiloride-sensitive, growth factor-activatable Na/H exchanger (NHE-1) is a ubiquitous mammalian protein that is involved in the regulation of intracellular pH and cell volume. We have determined the intron/exon boundaries and the transcription initiation sites and have characterized a portion of the 5'-flanking regulatory region of the human NHE-1 gene. The Na/H exchanger gene spans approximately 70 kilobases. The coding region is divided into 12 exons and 11 introns, one of which is 41.5 kilobases in length. The first exon contains the entire 5'-noncoding region, which is 786 bases long, and 352 bases of the coding sequence. Primer extension identified two discrete start sites for RNA polymerase. 1377 bases of the 5'-regulatory region were sequenced. The promoter/enhancer region is characterized by a TATA box, four GC boxes, two CAAT boxes, five CACCC boxes, three Ap-1 sites, a cyclic AMP response element, and four partial glucocorticoid response elements. Promoter activities of a 313- and a 1441-base pair fragment containing the TATA box were demonstrated by their ability to direct chloramphenicol acetyltransferase expression when transiently expressed in fibroblasts.

Original languageEnglish (US)
Pages (from-to)10813-10819
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number17
StatePublished - Sep 6 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Miller, R. T., Counillon, L., Pages, G., Lifton, R. P., Sardet, C., & Pouysségur, J. (1991). Structure of the 5'-flanking regulatory region and gene for the human growth factor-activatable Na/H exchanger NHE-1. Journal of Biological Chemistry, 266(17), 10813-10819.