کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2818985 | 1569895 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Abundant expression of Kallikrein 1 gene in human keratinocytes was mediated by GATA3 Abundant expression of Kallikrein 1 gene in human keratinocytes was mediated by GATA3](/preview/png/2818985.png)
Among Tissue kallikrein genes (KLKs), KLK1 is abundantly expressed in human skin. Although its putative promoter is known to have various cis-elements, they have not been functionally tested. In the present study, the regulation mechanism of KLK1 promoter supporting such abundant expression was examined. Luciferase assay targeting the KLK1 promoter (nucleotide − 1153/+ 40 from the major transcriptional start site) was performed on NHEK human keratinocyte. − 954/− 855, − 428/− 236, and − 100/+ 40 had the induction activity. The motif search program failed to find unique binding motifs in − 428/− 236, whereas both − 954/− 855 and − 100/+ 40 had a unique GATAs binding motif. Electrophoretic mobility shift assay (EMSA) and DNA footprinting confirmed the binding of NHEK nuclear protein to these motifs that were supershifted by anti-GATA3 antibody. Among GATA isoforms, GATA3 alone could be amplified in RNA obtained from NHEK. Moreover, introduction of GATA3 into fibroblastic NIH3T3 cells enhanced the activity of KLK1 promoter containing − 954/+ 40, while that of GATA3 dominant negative mutant to NHEK cells impaired the same promoter's activity. Thus, GATA3 was found to bind the site located at − 954/− 855 and to be a key regulator of abundant KLK1 expression in human keratinocyte.
Journal: Gene - Volume 436, Issues 1–2, 1 May 2009, Pages 121–127