ZENON, a novel POZ Kruppel-like DNA binding protein associated with differentiation and/or survival of late postmitotic neurons
ZENON, a novel POZ Kruppel-like DNA binding protein associated with differentiation and/or survival of late postmitotic neurons
复制标题
DOI：
10.1128/mcb.25.5.1713-1729.2005
复制
发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Mallet, J
中科院分区：
文献类型：
--
作者：
Kiefer, H;Chatail-Hermitte, F;Mallet, J
大鼠酪氨酸羟化酶基因启动子包含一个E-box/dyad基序和一个八聚体和七聚体元件，这些元件可以被神经系统发育过程中高度表达的转录因子类识别。在单杂交遗传筛选中，我们使用这些位点作为靶点来分离编码大脑中存在的新转录因子的cDNA。我们确定了ZENON，一种新的大鼠POZ蛋白，含有两簇Kruppel样锌指，并提出了几个转录因子的功能。在用cDNA瞬时转染后，在细胞核中发现ZENON。N-末端锌指簇包含与E盒相互作用的DNA结合结构域。共转染实验表明，ZENON诱导酪氨酸羟化酶启动子活性。与其他POZ蛋白不同，ZENON POZ结构域不需要激活转录或自结合。在胚胎神经管中，ZENON表达仅限于已经实现有丝分裂并参与神经元分化的晚期阶段（晚期有丝分裂后神经元）的神经元。ZENON神经元表达持续存在于成人大脑中;因此，ZENON可以被认为是成熟神经元的标志物。我们建议，ZENON参与泛神经元功能的维持和/或成熟神经元的存活。
The rat tyrosine hydroxylase gene promoter contains an E-box/dyad motif and an octameric and heptameric element that may be recognized by classes of transcription factors highly expressed during nervous system development. In a one-hybrid genetic screen, we used these sites as targets to isolate cDNAs encoding new transcription factors present in the brain. We identified ZENON, a novel rat POZ protein that contains two clusters of Kruppel-like zinc fingers and that presents several features of a transcription factor. ZENON is found in nuclei following transient transfection with the cDNA. The N-terminal zinc finger cluster contains a DNA binding domain that interacts with the E box. Cotranfection experiments revealed that ZENON induces tyrosine hydroxylase promoter activity. Unlike other POZ proteins, the ZENON POZ domain is not required for either activation of transcription or self-association. In the embryonic neural tube, ZENON expression is restricted to neurons that have already achieved mitosis and are engaged in late stages of neuronal differentiation (late postmitotic neurons). ZENON neuronal expression persists in the adult brain; therefore, ZENON can be considered a marker of mature neurons. We propose that ZENON is involved in the maintenance of panneuronal features and/or in the survival of mature neurons.