Structure and expression of the ATFa gene

Structure and expression of the ATFa gene
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DOI:
10.1074/jbc.271.47.29589
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发表时间:
1996-11-22
影响因子:
4.8
通讯作者:
Kedinger, C
Kedinger, C
中科院分区:
生物学2区
文献类型:
--
作者:
Goetz, J;Chatton, B;Kedinger, C

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人类ATFa蛋白属于ATF/CREB转录因子家族,我们之前已经证明它们介导最大的Ela蛋白的转录激活,并且可以与Jun/Fos家族成员异二聚化,ATFa蛋白还被发现与JNK2紧密相关,这是一种应激激活激酶。我们现在报道了ATFa基因的结构,该基因位于12号染色体(12q13带)。序列分析显示,ATFa异构体是由选择性剪接供体位点产生的,发现了一个类似200个碱基对的最小启动子区域,保留了几乎全部的转录活性,通过DNase I足迹在富含gc的片段中描绘了潜在转录因子的结合位点。表达研究表明,ATFa在转染细胞的细胞核中积累,并且在亮氨酸拉链结构域附近定义了核定位信号。通过与小鼠ATFa序列杂交发现,低水平的ATFa mrna在胎儿或成年小鼠中普遍存在,并在特定组织(如鳞状上皮和特定脑细胞层)中表达增强。讨论了ATFa、ATF-2和Jun在脑内相似部位共表达的可能意义。
The human ATFa proteins belong to the ATF/CREB family of transcription factors, We have previously shown that they mediate the transcriptional activation by the largest Ela protein and can heterodimerize with members of the Jun/Fos family, ATFa proteins have also been found tightly associated with JNK2, a stress-activated kinase. We now report on the structure of the ATFa gene, which mapped to chromosome 12 (band 12q13). Sequence analysis revealed that ATFa isoforms are generated by alternative splice donor site usage, A minimal promoter region of similar to 200 base pairs was identified that retained nearly full transcriptional activity, Binding sites for potential transcription factors were delineated within a GC-rich segment by DNase I foot printing. Expression studies revealed that ATFa accumulates in the nuclei of transfected cells, and the nuclear localization signal was defined next to the leucine zipper domain. As revealed by hybridization with mouse ATFa sequences, low levels of ATFa mRNAs were ubiquitously distributed in fetal or adult mice, with enhanced expression in particular tissues, like squamous epithelia and specific brain cell layers. The possible significance of coexpression of ATFa, ATF-2, and Jun at similar sites in the brain is discussed.