Hong Seok Jong, Choi Hyun Jin, Hong Sunghoi, Huh Youngbuhm, Chae Han, Kim Kwang-Soo
Molecular Neurobiology Laboratory, MRC215, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
Neurochem Res. 2008 Sep;33(9):1821-31. doi: 10.1007/s11064-008-9639-3. Epub 2008 Mar 13.
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.
GATA-3是一种锌指转录因子，在发育过程中表达于T细胞谱系以及神经系统。在本研究中，我们报告称，在原代神经嵴干细胞（NCSC）培养中，GATA-3的强制表达导致表达多巴胺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结构域强有力地反式激活去甲肾上腺素（NA）合成的DBH基因的启动子功能；一个在-62至-32 bp处，另一个在-891至-853 bp处。令人惊讶的是，这些结构域均不包含GATA-3结合位点，但分别包含转录因子Sp1和AP4的结合基序。体外和体内的蛋白质-蛋白质相互作用分析以及染色质免疫沉淀（ChIP）试验表明，GATA-3通过与这些转录因子的物理相互作用来发挥其转录调节功能。
