Lee J H, Shimojo M, Chai Y G, Hersh L B
Department of Biochemistry, University of Kentucky, Chandler Medical Center, Lexington 40536-0298, USA.
Brain Res Mol Brain Res. 2000 Aug 14;80(1):88-98. doi: 10.1016/s0169-328x(00)00129-7.
REST4 is a neuron specific truncated form of the transcription factor REST/NRSE derived by alternative splicing. REST4 was previously shown to block the repressor activity of REST/NRSF by forming a hetero-oligomer, Shimojo et al. [Mol. Cell. Biol. 19 (1999) 6788-6795]. A series of deletion mutants have now been used to characterize REST4 in terms of its structure and DNA binding. REST4 was found to be O-glycosylated between between residues 87 and 152. Binding of REST4 to the cholinergic RE-1/NRSE was approximately 1/10 to 1/20 as strong as full length REST/NRSF. DNA binding was enhanced by deletion of the first 86 residues and was found to require all four of the C-terminal zinc fingers as well as a twelve amino acid sequence preceding the first of these zinc fingers. REST4 can form homo-oligomers, however only the monomer was found to bind to DNA. REST4 binds to the 3' sequence of the cholinergic NRSE suggesting an anti-parallel orientation of the protein to the DNA.
REST4是转录因子REST/NRSE通过可变剪接产生的一种神经元特异性截短形式。先前的研究表明，Shimojo等人[《分子与细胞生物学》19(1999)6788 - 6795]发现REST4通过形成异源寡聚体来阻断REST/NRSF的阻遏活性。现在，一系列缺失突变体已被用于从结构和DNA结合方面对REST4进行表征。研究发现，REST4在第87位和第152位残基之间存在O-糖基化。REST4与胆碱能RE-1/NRSE的结合强度约为全长REST/NRSF的1/10至1/20。删除前86个残基可增强DNA结合，并且发现其需要所有四个C末端锌指以及第一个锌指之前的一个十二氨基酸序列。REST4可以形成同源寡聚体，但只有单体被发现能与DNA结合。REST4与胆碱能NRSE的3'序列结合，这表明该蛋白质与DNA呈反平行方向。
