PMID- 10198359
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20190129
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 4
DP  - 1999 Apr
TI  - Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and
      Sp3.
PG  - L614-24
LID - 10.1152/ajplung.1999.276.4.L614 [doi]
AB  - 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 Sp1 and Sp3 at birth explains perinatal
      downregulation of ClC-2 in the lung.
FAU - Chu, S
AU  - Chu S
AD  - Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore,
      Maryland 21287-2533, USA. shijian@welchlink.welch.jhu.edu
FAU - Blaisdell, C J
AU  - Blaisdell CJ
FAU - Liu, M Z
AU  - Liu MZ
FAU - Zeitlin, P L
AU  - Zeitlin PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Chloride Channels)
RN  - 0 (ClC-2 chloride channels)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (SP3 protein, human)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Sp3 protein, rat)
RN  - 0 (Transcription Factors)
RN  - 148710-94-5 (Sp3 Transcription Factor)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Aging
MH  - Amino Acid Sequence
MH  - Animals
MH  - Animals, Newborn
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Chloride Channels/biosynthesis/chemistry/*genetics
MH  - DNA-Binding Proteins/*metabolism
MH  - Embryonic and Fetal Development/*physiology
MH  - Fetus
MH  - *Gene Expression Regulation, Developmental
MH  - Humans
MH  - Luciferases/genetics
MH  - Lung/embryology/growth & development/*physiology
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/biosynthesis/chemistry/*genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Restriction Mapping
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Sp1 Transcription Factor/*metabolism
MH  - Sp3 Transcription Factor
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - 10.1152/ajplung.1999.276.4.L614 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Apr;276(4):L614-24. doi: 10.1152/ajplung.1999.276.4.L614.