Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain

In this study, we investigated the binding characteristics of MeCP2 in recognizing unmethylated 5′-CAC/GTG-3′ motif containing DNA by binding and structural studies. We found that MeCP2-MBD binds to MARs DNA with a comparable binding affinity to mCG DNA, and the MeCP2-CAC/GTG complex structure revealed that MeCP2 residues R111 and R133 form base-specific interactions with the GTG motif. For comparison, we also determined crystal structures of the MeCP2-MBD bound to mCG and mCAC/GTG DNA, respectively. Together, these crystal structures illustrate the adaptability of the MeCP2-MBD toward the GTG motif as well as the mCG DNA, and also provide structural basis of a biological role of MeCP2 as a transcription activator and its disease implications in Rett syndrome.Graphical abstract

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - July 27, 2019 Category: Genetics & Stem Cells Source Type: research