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

Takatoshi Morinaga, Atsushi Enomoto, Yohei Shimono, Fumiko Hirose, Naoyuki Fukuda, Atsushi Dambara, Mayumi Jijiwa, Kumi Kawai, Katsunori Hashimoto, Masatoshi Ichihara, Naoya Asai, Yoshiki Murakumo, Seiichi Matsuo, Masahide Takahashi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4191-4201
Number of pages11
JournalNucleic acids research
Volume33
Issue number13
DOIs
Publication statusPublished - 2005

All Science Journal Classification (ASJC) codes

  • Genetics

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