GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.
GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.
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DOI：
10.1093/nar/gki734
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发表时间：
2005
影响因子：
14.9
通讯作者：
Takahashi, M
中科院分区：
文献类型：
--
作者：
Morinaga, T;Enomoto, A;Shimono, Y;Hirose, F;Fukuda, N;Dambara, A;Jijiwa, M;Kawai, K;Hashimoto , K;Ichihara, M;Asai, N;Murakumo, Y;Matsuo, S;Takahashi, M
RET酪氨酸激酶受体及其配体胶质细胞源性神经营养因子（GDNF）是肾脏和神经发育的关键调节因子。研究表明，RET激活多种下游信号级联，包括RAS/促分裂原活化蛋白激酶和磷脂酰肌醇-3-激酶（PI 3-K）/AKT通路。然而，特异于RET触发信号的核靶点仍然难以捉摸。我们以前已经确定了一种新的锌指蛋白，GZF 1，其表达在GDNF/RET信号转导过程中诱导，并可能在肾分支形态发生中发挥作用。本文报道了GZF-1的DNA结合特性及其潜在的靶基因。使用循环扩增和靶点选择技术，确定GZF 1结合的共有DNA序列。该序列位于HOXA 10基因的5′调控区。电泳迁移率变动分析表明，GZF 1特异性结合到确定的共识序列，并抑制从HOXA 10基因调控元件的荧光素酶基因的转录。因此，这些研究结果表明，GZF 1可以调节HOXA 10基因的空间和时间的表达，在形态发生中发挥作用。
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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影响因子：
4.8
作者：
Fukuda, N;Ichihara, M;Takahashi, M
通讯作者：
Takahashi, M
影响因子：
14.9
作者：
Kaplan, J;Calame, K
通讯作者：
Calame, K
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11.4
作者：
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通讯作者：
Verrijzer, CP
影响因子：
64.8
作者：
Moore, MW;Klein, RD;Rosenthal, A
通讯作者：
Rosenthal, A
影响因子：
14.9
作者：
POLLOCK, R;TREISMAN, R
通讯作者：
TREISMAN, R