CIL:7106, Homo sapiens, neuron. In Cell Image Library

The protein MeCP2 binds to symmetrically methylated CpG dinucleotides and is thought to transmit the (generally) repressive signals encoded in DNA methylation patterns. Mutations in MeCP2 lead to Rett syndrome. Here, MeCP2-DNA complexes have been imaged by AFM (Digital Instruments Nanoscope) in air using human MeCP2 and an 828 bp DNA sequence containing several methylated CpGs. MeCP2 molecules appear as bright particles in AFM images. Volume measurements of the complexes suggest that MeCP2 monomers (circular particles) and dimers (larger elliptical particles) are present and suggest that MeCP2 binds DNA cooperatively. Other images in the grouped set show looped structures and large complexes containing multiple DNA strands and MeCP2 molecules. These configurations are likely promoted by the multiple independent DNA-binding domains of MeCP2 and relevant to the in vivo interactions between MeCP2 and chromatin.

甲基化CpG结合蛋白2（MeCP2）可与对称甲基化的CpG二核苷酸结合，据信其能够传递由DNA甲基化模式编码的（通常为）抑制性信号。MeCP2的突变会引发雷特综合征。本研究中，研究人员利用人源MeCP2与一段包含多个甲基化CpG位点的828碱基对（bp）DNA序列，通过原子力显微镜（Atomic Force Microscopy, AFM）（Digital Instruments Nanoscope型号）在空气环境下对MeCP2-DNA复合物进行了成像。在AFM图像中，MeCP2分子呈现为明亮的颗粒状结构。对复合物的体积测定结果表明，体系中存在MeCP2单体（圆形颗粒）与二聚体（尺寸更大的椭圆形颗粒），且提示MeCP2以协同方式与DNA结合。该组影像集中的其他图像则显示出环化结构，以及包含多条DNA链与多个MeCP2分子的大型复合物。此类结构极有可能由MeCP2所具备的多个独立DNA结合结构域所介导形成，且与MeCP2在体内与染色质的相互作用密切相关。