Stat3 is involved in control of MASP2 gene expression.
Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 to be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity.
Unterberger
Claudia
C
Clinical Cooperation Group Inflammatory Lung Diseases (GSF-National Research Center for Environment and Health, Asklepios Fachkliniken), Gauting, Germany.
Hanson
Steven
S
Klingenhoff
Andreas
A
Oesterle
Daniela
D
Frankenberger
Marion
M
Endo
Yuichi
Y
Matsushita
Misao
M
Fujita
Teizo
T
Schwaeble
Wilhelm
W
Weiss
Elisabeth H
EH
Ziegler-Heitbrock
Löms
L
Stover
Cordula
C
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D050796:STAT3 Transcription Factor; C491340:MASP-2 protein, mouse; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases