PMID- 10625644
OWN - NLM
STAT- MEDLINE
DCOM- 20000218
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 2
DP  - 2000 Jan 14
TI  - GATA-6 activates transcription of surfactant protein A.
PG  - 1043-9
AB  - Surfactant protein A (SP-A) is a member of the collectin family of innate host
      defense molecules expressed primarily in respiratory epithelial cells of the
      lung. SP-A concentrations are influenced by both cell-specific and ubiquitous
      nuclear proteins that regulate SP-A gene transcription in a cell-selective and
      temporally regulated manner. In this work, a consensus GATA-binding site (GBS)
      was identified at positions -69 to -64 of the mouse SP-A gene. The
      transcriptional activity of wild-type SP-A reporter constructs in HeLa cells was 
      increased 5-10-fold when cotransfected with a GATA-6 expression plasmid. Deletion
      of the GBS completely blocked transactivation by GATA-6. Transfection of a
      construct expressing GATA-6-engrailed fusion protein inhibited basal expression
      of the SP-A/chloramphenicol acetyltransferase construct in MLE-15 cells. Nuclear 
      extract proteins from MLE-15 cells bound to the GBS in the mouse SP-A gene, and a
      supershifted band was detected with a GATA-6-specific antibody. Transactivation
      of the wild-type SP-A constructs by GATA-6 increased transcriptional activity
      7-10-fold, whereas thyroid transcription factor-1 (TTF-1) increased the activity 
      of these constructs 12-18-fold. The effects of cotransactivating with both GATA-6
      and TTF-1 expression constructs were additive. However, mutation of the
      TTF-1-binding sites alone or in combination decreased GATA-6 transactivation.
      Likewise, mutation of the GBS blocked TTF-1 activation of the SP-A promoter. In
      situ hybridization demonstrated GATA-6 mRNA in the peripheral epithelial cells of
      fetal mouse lung, consistent with the sites of SP-A expression. GATA-6 is
      expressed in respiratory epithelial cells and binds to a cis-acting element in
      the SP-A gene promoter, activating the transcriptional activity of the gene.
FAU - Bruno, M D
AU  - Bruno MD
AD  - Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati,
      Ohio 45229-3039, USA.
FAU - Korfhagen, T R
AU  - Korfhagen TR
FAU - Liu, C
AU  - Liu C
FAU - Morrisey, E E
AU  - Morrisey EE
FAU - Whitsett, J A
AU  - Whitsett JA
LA  - eng
GR  - HL28623/HL/NHLBI NIH HHS/United States
GR  - HL58795/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GATA6 Transcription Factor)
RN  - 0 (GATA6 protein, human)
RN  - 0 (Gata6 protein, mouse)
RN  - 0 (Glycoproteins)
RN  - 0 (NKX2-1 protein, human)
RN  - 0 (Nkx2-1 protein, mouse)
RN  - 0 (Nkx2-1 protein, rat)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteolipids)
RN  - 0 (Pulmonary Surfactant-Associated Protein A)
RN  - 0 (Pulmonary Surfactant-Associated Proteins)
RN  - 0 (Pulmonary Surfactants)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thyroid Nuclear Factor 1)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Conserved Sequence
MH  - DNA-Binding Proteins/*metabolism
MH  - GATA6 Transcription Factor
MH  - *Gene Expression Regulation
MH  - Glycoproteins/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Lung/embryology/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Proteins/metabolism
MH  - Proteolipids/*genetics
MH  - Pulmonary Surfactant-Associated Protein A
MH  - Pulmonary Surfactant-Associated Proteins
MH  - Pulmonary Surfactants/*genetics
MH  - Rats
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Recombinant Proteins/biosynthesis
MH  - Respiratory Mucosa/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - Thyroid Nuclear Factor 1
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Zinc Fingers
EDAT- 2000/01/08 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/08 09:00
PHST- 2000/01/08 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/08 09:00 [entrez]
AID - 10.1074/jbc.275.2.1043 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 14;275(2):1043-9. doi: 10.1074/jbc.275.2.1043.