Transcription factor GATA-3 regulates the transcriptional activity of dopamine β-hydroxylase by interacting with Sp1 and AP4
Transcription factor GATA-3 regulates the transcriptional activity of dopamine β-hydroxylase by interacting with Sp1 and AP4
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DOI：
10.1007/s11064-008-9639-3
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Kim, Kwang-Soo
中科院分区：
文献类型：
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作者：
Hong, Seok Jong;Choi, Hyun Jin;Kim, Kwang-Soo
GATA-3是一种锌指转录因子，在发育过程中在T细胞谱系和神经系统中表达。在这项研究中，我们报道了强迫表达GATA-3导致原代神经嵴干细胞（NCSC）培养中表达多巴胺β -羟化酶（DBH）的神经元数量增加，这表明DBH基因可能是GATA-3的下游靶基因。GATA-3通过两个特定的上游启动子域强有力地激活去甲肾上腺素（NA）合成DBH基因的启动子功能；一个在-62至-32 bp，另一个在-891至-853 bp。令人惊讶的是，这些结构域都不包含GATA-3结合位点，但分别包含转录因子Sp1和AP4的结合基序。体外和体内蛋白相互作用分析以及染色质免疫沉淀（ChIP）实验表明，GATA-3通过与这些转录因子的物理相互作用来影响其转录调节功能。
GATA-3 is a zinc finger transcription factor that is expressed in T cell lineages as well as in the nervous system during development. In this study, we report that forced expression of GATA-3 resulted in an increased number of dopamine beta-hydroxylase (DBH)-expressing neurons in primary neural crest stem cell (NCSC) culture, suggesting that the DBH gene may be a downstream target gene of GATA-3. GATA-3 robustly transactivates the promoter function of the noradrenaline (NA)-synthesizing DBH gene, via two specific upstream promoter domains; one at -62 to -32 bp and the other at -891 to -853 bp. Surprisingly, none of these domains contain GATA-3 binding sites but encompass binding motifs for transcription factors Sp1 and AP4, respectively. Protein-protein interaction analyses both in vitro and in vivo and chromatin immunoprecipitation (ChIP) assays showed that GATA-3 effects its transcriptional regulatory function through physical interactions with these transcription factors.