PMID- 9545353
OWN - NLM
STAT- MEDLINE
DCOM- 19980521
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 16
DP  - 1998 Apr 17
TI  - Comparison of promoters for the murine and human P-selectin genes suggests 
      species-specific and conserved mechanisms for transcriptional regulation in 
      endothelial cells.
PG  - 10058-67
AB  - P-selectin, an adhesion receptor for leukocytes, is constitutively expressed in 
      megakaryocytes and endothelial cells. Tumor necrosis factor-alpha (TNF-alpha) or 
      lipopolysaccharide (LPS) increases synthesis of P-selectin in murine but not in 
      human endothelial cells. To identify potential species-specific and conserved 
      mechanisms for regulation of expression of P-selectin, we cloned the 5'-flanking 
      region of the murine P-selectin gene and compared its features with those 
      previously reported for the human gene. The murine and human genes shared 
      conserved Stat-like, Hox, Ets, GATA, and GT-IIC elements. In the murine gene, a 
      conserved GATA element bound to GATA-2 and functioned as a positive regulatory 
      element, whereas a conserved Ets element bound to GA-binding protein and 
      functioned as a negative regulatory element. Significantly, the murine P-selectin 
      gene had several features not found in the human gene. These included an 
      insertion from -987 to -649 that contained tandem GATA and tandem AP1-like 
      sequences, which resembled enhancers in beta-globin locus control regions. Both 
      tandem elements bound specifically to nuclear proteins. The murine gene lacked 
      the unique kappaB site specific for p50 or p52 homodimers found in the human 
      gene. Instead, it contained two tandem kappaB elements and a variant activating 
      transcription factor/cAMP response element site, which closely resembled sites in 
      the E-selectin gene that are required for TNF-alpha- or LPS-inducible expression. 
      TNF-alpha or LPS augmented expression of a reporter gene driven by the murine, 
      but not the human, P-selectin promoter in transfected endothelial cells. 
      Deletional analysis of the murine 5'-flanking region revealed several sequences 
      that were required for either constitutive or inducible expression. These data 
      suggest that both species-specific and conserved mechanisms regulate 
      transcription of the human and murine P-selectin genes.
FAU - Pan, J
AU  - Pan J
AD  - Department of Medicine, W. K. Warren Medical Research Institute, University of 
      Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
FAU - Xia, L
AU  - Xia L
FAU - McEver, R P
AU  - McEver RP
LA  - eng
SI  - GENBANK/AF031662
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Lipopolysaccharides)
RN  - 0 (P-Selectin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Aorta
MH  - Base Sequence
MH  - Binding Sites
MH  - Cattle
MH  - Cell Line
MH  - Cells, Cultured
MH  - Conserved Sequence
MH  - Endothelium, Vascular/*metabolism
MH  - Enhancer Elements, Genetic
MH  - *Gene Expression Regulation/drug effects
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Luciferases/biosynthesis
MH  - Mice
MH  - Molecular Sequence Data
MH  - P-Selectin/*biosynthesis/*genetics
MH  - *Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Regulatory Sequences, Nucleic Acid
MH  - Restriction Mapping
MH  - Sequence Alignment
MH  - Sequence Deletion
MH  - Sequence Homology, Nucleic Acid
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1998/05/23 00:00
MHDA- 1998/05/23 00:01
CRDT- 1998/05/23 00:00
PHST- 1998/05/23 00:00 [pubmed]
PHST- 1998/05/23 00:01 [medline]
PHST- 1998/05/23 00:00 [entrez]
AID - S0021-9258(18)46236-9 [pii]
AID - 10.1074/jbc.273.16.10058 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Apr 17;273(16):10058-67. doi: 10.1074/jbc.273.16.10058.