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Nucleic Acids Research 2005 33(13):4191-4201; doi:10.1093/nar/gki734
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Published online 26 July 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region

Takatoshi Morinaga1,2, Atsushi Enomoto1, Yohei Shimono1, Fumiko Hirose3, Naoyuki Fukuda1,2, Atsushi Dambara1,2, Mayumi Jijiwa1, Kumi Kawai4, Katsunori Hashimoto5, Masatoshi Ichihara5, Naoya Asai1, Yoshiki Murakumo1, Seiichi Matsuo2 and Masahide Takahashi1,4,*

1Department of Pathology, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan 2Department of Internal Medicine, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan 3The Department of Life Science, Graduate School of Science, Himeji Institute of Technology 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan 4The Division of Molecular Pathology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan 5The Department of Medical Technology, Nagoya University School of Health Sciences 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan

*To whom correspondence should be addressed. Tel: +81 52 744 2092; Fax: +81 52 744 2098; Email: mtakaha{at}med.nagoya-u.ac.jp

Received March 31, 2005. Revised July 8, 2005. Accepted July 8, 2005.

The RET tyrosine kinase receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF) are critical regulators of renal and neural development. It has been demonstrated that RET activates a variety of downstream signaling cascades, including the RAS/mitogen-activated protein kinase and phosphatidylinositol-3-kinase(PI3-K)/AKT pathways. However, nuclear targets specific to RET-triggered signaling still remain elusive. We have previously identified a novel zinc finger protein, GZF1, whose expression is induced during GDNF/RET signaling and may play a role in renal branching morphogenesis. Here, we report the DNA binding property of GZF1 and its potential target gene. Using the cyclic amplification and selection of targets technique, the consensus DNA sequence to which GZF1 binds was determined. This sequence was found in the 5' regulatory region of the HOXA10 gene. Electrophoretic mobility shift assay revealed that GZF1 specifically binds to the determined consensus sequence and suppresses transcription of the luciferase gene from the HOXA10 gene regulatory element. These findings thus suggest that GZF1 may regulate the spatial and temporal expression of the HOXA10 gene which plays a role in morphogenesis.


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