Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA, New England Biolabs, 240 County Road, Ipswich, MA 01938, USA and Department of Medical Microbiology and Immunology and Program in Bioinformatics, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Nucleic Acids Res. 2014 Apr;42(8):4859-67. doi: 10.1093/nar/gku134. Epub 2014 Feb 11.
Transcription factor Krüppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Krüppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 Å resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg-Glu pair.
转录因子 Krüppel 样因子 4（Klf4）是指导细胞重编程的因子之一，它识别特定的 G/C 丰富序列内的 CpG 二核苷酸（无论是甲基化的还是未修饰的）。小鼠 Klf4 DNA 结合域与甲基化 DNA 的结合亲和力仅略强于未修饰的寡核苷酸。用 1.85Å 分辨率确定了与完全甲基化 DNA 结合的小鼠 Klf4 的 C 端三个 Krüppel 样锌指（ZnF）的结构。精氨酸和谷氨酸与甲基相互作用。与最近描述的另外两个具有甲基化 DNA 的 ZnF 蛋白复合物的结构进行比较，我们提出了 C2H2 ZnF 蛋白识别甲基化 CpG 的共同原则，其中涉及空间保守的 Arg-Glu 对。
