Hu, Kanghong and Fink, Marina and Froh, Matthias and Gaebele, Erwin and Hellerbrand, Claus and Muehlbauer, Marcus and Wiest, Reiner and Schoelmerich, Juergen and Schnabl, Bernd (2005) Characterization of the human zinc finger protein 267 promoter: Essential role of nuclear factor Y. BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1729 (1). pp. 14-23. ISSN 0167-4781,
Full text not available from this repository. (Request a copy)Abstract
Liver fibrosis results from an excessive deposition of extracellular matrix proteins secreted by activated hepatic stellate cells (HSCs). The activation process is accompanied by an increased activity of various transcription factors, including zinc finger protein 267 (ZNF267). Recently, ZNF267 has been shown to modulate gene expression and to function as a transcriptional repressor. MMP-10 was identified as a target gene; its gene expression and promoter activity are inhibited by ZNF267, which might promote liver fibrogenesis through diminished matrix degradation. However, the transcriptional regulation of the ZNF267 gene is unknown. In the present study, we have cloned and characterized the human ZNF267 promoter containing a 1.5 kb fragment of the 5'-flanking region (-1414/+173). The ZNF267 gene has a TATA-less promoter with multiple transcription initiation sites. Analysis of serial 5'-deletions of luciferase reporter constructs revealed a minimal promoter between -72 and +173 bp. Mutational analysis of putative regulatory elements indicated that a CCAAT box within this region was essential for ZNF267 promoter activity. Electrophoretic mobility shift assays demonstrated that transcription factor nuclear factor Y (NF-Y) bound to the CCAAT box. In co-transfection experiments, NF-YA increased the promoter activity of ZNF267. In conclusion, our results suggest that the binding site for NF-Y is critical for ZNF267 gene regulation and, herewith, the activation of this transcriptional factor may play an important role in the activation process of HSCs and in liver fibrosis. (c) 2005 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; NF-Y; TRANSCRIPTIONAL REPRESSION; HYDROGEN-PEROXIDE; BINDING-ACTIVITY; EXPRESSION; IDENTIFICATION; ACTIVATION; INITIATION; INHIBITION; Kruppel-like zinc finger protein; hepatic stellate cell; promoter; gene regulation; nuclear factor Y; CCAAT box |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2021 12:42 |
| Last Modified: | 11 May 2021 12:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36121 |
Actions (login required)
 |
View Item |
