A distant upstream region of the rat multipartite Na(+)-Ca(2+) exchanger NCX1 gene promoter is sufficient to confer cardiac-specific expression

Mech Dev. 2001 Dec;109(2):267-79. doi: 10.1016/s0925-4773(01)00548-2.

Abstract

The Na(+)-Ca(2+) exchanger (NCX) regulates intracellular calcium homeostasis. We report on an upstream region of the rat NCX1 multipartite promoter that is active in cardiac myocytes. Although inactive in most non-cardiac cell lines, its activity can be rescued by cotransfection with GATA-4 and -6, but not GATA-5 transcription factors. In transgenic mice and similar to endogenous NCX1 mRNA expression, the upstream promoter region directs uniform beta-galactosidase expression in cardiac myocytes from approximately 7.75dpc. In adult mouse hearts, promoter activity is, however, significantly reduced and heterogeneous, except in the conduction system (sinoatrial and atrioventricular node, atrioventricular bundles). The upstream NCX1 promoter region thus directs appropriate spatial and temporal control of cardiac expression throughout development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Western
  • COS Cells
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Exons
  • GATA4 Transcription Factor
  • GATA5 Transcription Factor
  • GATA6 Transcription Factor
  • Genes, Reporter
  • Lac Operon
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism*
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium-Calcium Exchanger / chemistry
  • Sodium-Calcium Exchanger / genetics*
  • Time Factors
  • Tissue Distribution
  • Transcription Factors / metabolism
  • Transfection
  • beta-Galactosidase / metabolism

Substances

  • DNA-Binding Proteins
  • GATA4 Transcription Factor
  • GATA5 Transcription Factor
  • GATA6 Transcription Factor
  • Gata5 protein, mouse
  • Gata5 protein, rat
  • Gata6 protein, mouse
  • RNA, Messenger
  • Sodium-Calcium Exchanger
  • Transcription Factors
  • sodium-calcium exchanger 1
  • DNA
  • beta-Galactosidase