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Expression control of the ADAMTS16 gene by the Wilms' tumor transcription factor WT1
Author(s) -
Jacobi Charlotte Louise Justine,
Kirschner Karin Michaela,
Scholz Holger
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.662.5
Subject(s) - wilms' tumor , transcription factor , gene , cancer research , wilms tumour , biology , genetics
The ADAMTS16 gene ( a d isintegrin a nd m etalloproteinase domain with t hrombo s pondin motifs) encodes a metalloproteinase with unknown physiological function. Due to structural similarity with other ADAMTS family members one would predict a role for ADAMTS16 in extracellular matrix degradation and angiogenesis. The aim of this study was to investigate ADAMTS16 expression and to identify transcriptional pathways involved in its regulation. Immunohistochemistry revealed a co‐expression of ADAMTS16 and WT1 in the embryonic kidneys and gonads, which require WT1 for normal development. Knock‐down of WT1 in kidney‐derived M15 cells by RNA interference reduced ADAMTS16 mRNA by 90±3% compared to transfection with non‐targeting siRNA. A luciferase reporter construct containing the ADAMTS16 promoter was activated more than 3‐fold by transient co‐transfection of a WT1 expression construct. Chromatin immunoprecipitation detected interaction of WT1 protein with the ADAMTS16 promoter in cultured M15 cells. In silico analysis and electrophoretic mobility shift assays proved three WT1 binding elements in the ADAMTS16 promotor in proximity to the transcription start site. In conclusion, we identified WT1 as a potential transcriptional regulator of the ADAMTS16 gene. Furthermore, our results suggest an involvement of ADAMTS16 in tissue remodelling in the testis and ovary.