4.6 Article

Abundant expression of Kallikrein 1 gene in human keratinocytes was mediated by GATA3

Journal

GENE
Volume 436, Issue 1-2, Pages 121-127

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2009.02.002

Keywords

Kallikrein 1 gene; GATA3; Transcriptional regulation; Human keratinocyte

Funding

  1. Ministry of Science, Education [C-18590551]

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Among Tissue kallikrein genes (KLKs), KLK1 is abundantly expressed inhuman 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. (C) 2009 Elsevier B.V. All rights reserved.

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