Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1
Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1
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DOI：
10.1016/j.mce.2015.04.018
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发表时间：
2015-08-15
影响因子：
4.1
通讯作者：
Kataoka, Kohsuke
中科院分区：
文献类型：
--
作者：
Han, Song-iee;Tsunekage, Yukino;Kataoka, Kohsuke
编码锌指转录因子的Gata3基因的单倍不足与人类甲状旁腺功能减退、耳聋和肾发育不良（HDR）综合征相关。然而，Gata3在甲状旁腺转录调控中的作用还不清楚。在这项研究中，我们表明Gata3激活甲状旁腺激素（PTH）的转录，该激素由甲状旁腺分泌，对调节血清钙和磷酸盐稳态至关重要。Gata3与Gcm 2和MafB（甲状旁腺发育的两种已知转录调节因子）相互作用，并协同刺激PTH启动子。位于PTH启动子近端区域的SP1结合元件（GC盒）对于Gata3激活转录至关重要。此外，普遍存在的转录因子SP1也与Gata3以及MafB和Gcm 2相互作用，并且HDR综合征相关的Gata3突变体在激活PTH启动子方面有缺陷。这些结果表明Gata3是PTH基因表达的关键调节因子。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans. However, the roles of Gata3 in transcriptional regulation in the parathyroid glands are not well-understood. In this study, we show that Gata3 activates transcription of parathyroid hormone (PTH), which is secreted from parathyroid glands and is critical for regulating serum calcium and phosphate homeostasis. Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. An SP1-binding element (GC box) located within the PTH-promoter proximal region was critical for activating transcription by Gata3. In addition, the ubiquitous transcription factor SP1 also interacted with Gata3 as well as MafB and Gcm2, and HDR syndromeassociated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression. (C) 2015 Elsevier Ireland Ltd. All rights reserved.