Methyl-CpG-binding protein 2 reads histone methylation via an aromatic cage to regulate gene expression and chromatin association.

ABSTRACT: Methyl-CpG binding protein 2 (MeCP2) is a DNA methylation reader, which is highly expressed in the central nervous system. Loss-of-function mutation of MeCP2, which impairs DNA binding, causes Rett syndrome, while gain of MeCP2 function causes MeCP2 duplication syndrome. MeCP2 functions as both a transcription activator and a repressor, but its full range of activity remains largely unknown. A recent study suggests that beyond DNA binding, MBD domain of MeCP2 also interacts with methylated lysine residues on histone H3 tail. In this study, we aimed to characterize the methyllysine-binding pocket of MeCP2-MBD. Structural analysis reveals the presence of an aromatic cage formed by five residues, namely, W104, F132, Y141, F142, and F155, where the trimethyllysine of H3K27me3 binds, as confirm

SUBMITTER: Padhan J 

PROVIDER: S-EPMC12857291 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature