Date Shoichi, Nibu Yutaka, Yanai Kazuyuki, Hirata Jun, Yagami Ken-Ichi, Fukamizu Akiyoshi
Center of Tsukuba Advanced Research Alliance, Institutes of Applied Biochemistry and Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Int J Mol Med. 2004 May;13(5):637-42.
We previously identified a regulatory element at the 3'-downstream region of the human angiotensinogen (hANG) gene. Using this element as a probe by the Southwestern screening, we isolated a cDNA clone, encoding Finb, a transcriptional activator with multiple zinc finger domains. The N-terminal zinc finger domain of Finb bound to the GGATGG sequence within the regulatory element. Unexpectedly, Finb repressed transcription dependent on the regulatory element. Inspection of the 5'-flanking region in the hANG promoter identified the GGATGG-like elements, which prompted us to examine the effect of Finb on the hANG promoter activity. We also found the two Finb binding elements in the 5'-flanking region of the hANG gene by the gel shift assay, both of which were necessary for transcriptional repression of the hANG promoter. These findings suggest that Finb functions as a sequence-specific transcriptional repressor of the hANG gene.
我们之前在人血管紧张素原（hANG）基因的3'下游区域鉴定出一个调控元件。通过西南筛选法将该元件用作探针，我们分离出一个cDNA克隆，其编码具有多个锌指结构域的转录激活因子Finb。Finb的N端锌指结构域与调控元件内的GGATGG序列结合。出乎意料的是，Finb抑制依赖于该调控元件的转录。对hANG启动子5'侧翼区域的检查发现了类似GGATGG的元件，这促使我们研究Finb对hANG启动子活性的影响。通过凝胶迁移实验，我们还在hANG基因的5'侧翼区域发现了两个Finb结合元件，二者对于hANG启动子的转录抑制都是必需的。这些发现表明，Finb作为hANG基因的序列特异性转录抑制因子发挥作用。
