Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B
Centre for Thrombosis and Vascular Research, School of Pathology, University of New South Wales, Sydney, New South Wales 2052, Australia.
J Biol Chem. 1999 Aug 13;274(33):23491-8. doi: 10.1074/jbc.274.33.23491.
We have identified a novel human zinc finger protein, hFOG-2, which is related to but distinct from the murine transcription factor Friend-of-GATA-1 (mFOG-1). The hFOG-2 gene was initially detected in K562 cells using a polymerase chain reaction approach with degenerate primers corresponding to zinc finger regions of mFOG-1. A murine homologue of hFOG-2 was also identified in the mouse expressed sequence tag data banks, indicating that a family of FOG genes exists in mammals. hFOG-2 appears to be widely expressed, while mFOG-1 is expressed primarily in erythroid and megakaryocytic cells and plays a fundamental role in the development of these lineages. Sequencing of the full-length hFOG-2 cDNA indicates that the interaction domains for transcription factors GATA-1 and mCtBP2 are both conserved and we have shown that this new FOG protein also physically interacts with these factors. We have demonstrated that hFOG-2, like mFOG-1, can act in concert with GATA-1 to activate gene expression from the p45 NF-E2 promoter region, but that it can also act to repress GATA-mediated activation of additional reporter constructs. Finally, we have identified a repression domain in hFOG-2 and show that repression is dependent upon the integrity of the mCtBP2 interaction motif Pro-Ile-Asp-Leu-Ser.
我们鉴定出一种新型人类锌指蛋白hFOG-2，它与鼠转录因子GATA-1的朋友（mFOG-1）相关但不同。使用与mFOG-1锌指区域对应的简并引物，通过聚合酶链反应方法最初在K562细胞中检测到hFOG-2基因。在小鼠表达序列标签数据库中也鉴定出hFOG-2的鼠同源物，表明哺乳动物中存在一个FOG基因家族。hFOG-2似乎广泛表达，而mFOG-1主要在红细胞和巨核细胞中表达，并在这些细胞系的发育中起基本作用。全长hFOG-2 cDNA的测序表明，转录因子GATA-1和mCtBP2的相互作用结构域都是保守的，并且我们已经表明这种新的FOG蛋白也与这些因子发生物理相互作用。我们已经证明，hFOG-2与mFOG-1一样，可以与GATA-1协同作用，从p45 NF-E2启动子区域激活基因表达，但它也可以抑制GATA介导的其他报告基因构建体的激活。最后，我们在hFOG-2中鉴定出一个抑制结构域，并表明抑制作用取决于mCtBP2相互作用基序Pro-Ile-Asp-Leu-Ser的完整性。
