title: GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.
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.
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Morinaga
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Fukuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Dambara
authors.forename: Mayumi
authors.initials: M
authors.lastname: Jijiwa
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawai
authors.forename: Katsunori
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichihara
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C480233:GZF1 protein, human; C480234:GZF1 protein, mouse; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C069634:HOXA10 protein, human; C092119:Hoxa10 protein, mouse