Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and Sp3

Shijian Chu, Carol J. Blaisdell, Min Zhi M. Liu, Pamela L. Zeitlin

Research output: Contribution to journalArticlepeer-review

Abstract

Mechanisms responsible for regulation of pulmonary epithelial chloride- channel expression in the perinatal period are under investigation to better understand normal lung development and airway disease pathogenesis. The ClC- 2 epithelial chloride channel is regulated by changes in pH and volume and is most abundant in lung during fetal development. In this study, we identify and sequence the ClC-2 promoter, which is GC rich and lacks a TATA box. By construction of a series of promoter-luciferase constructs, a 67-bp GC box- containing sequence in the promoter is shown to be critical to ClC-2 expression in primary and immortalized fetal lung epithelial cells. Electrophoretic mobility shift assays and antibody supershifts demonstrate that the Sp1 and Sp3 transcription factors are expressed in fetal lung nuclei and interact with the GC box sequences in the promoter. Immunoblotting techniques demonstrate that Sp1 and Sp3 are perinatally downregulated in the lung with the same temporal sequence as ClC-2 downregulation. This work suggests that Sp1 and Sp3 activate ClC-2 gene transcription and that reduction in Spl and Sp3 at birth explains perinatal downregulation of ClC-2 in the lung.

Original languageEnglish (US)
Pages (from-to)L614-L624
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number4 20-4
DOIs
StatePublished - Apr 1999

Keywords

  • Development
  • Epithelial cell
  • Gene expression
  • Ribonucleic acid polymerase II
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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