MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer

Abstract

DNA methylation is a key epigenetic mechanism that mediates gene expression and informs cellular identity. Methyl-CpG binding protein 2 (MeCP2) is a protein capable of recognizing and interpreting the methylated DNA code to bring about phenotypic outcomes through co-factor interactions. Altered DNA methylation patterns and MeCP2 function, therefore, disrupt cellular epigenetic homeostasis and contribute to human diseases. MeCP2 loss-of-function or amplification events are responsible for Rett syndrome and MECP2 duplication syndrome, respectively, where patients present with multisystem pathophysiology. Growing evidence suggests that MeCP2 contributes to immune dysregulation in these syndromes and is a key epigenetic regulator in additional inflammatory conditions. Research in past decades has functionally linked MeCP2 to tumorigenesis across cancer types, where it can support and inhibit oncogenic properties in a contextual manner. The precise mechanistic role of MeCP2 in non-neuronal and cancer models is underexplored. Here, we summarize the diverse epigenetic functionalities of MeCP2 influenced by its molecular structure, regulation, and co-factor interactions and discuss how MeCP2 regulates immune homeostasis and tumorigenesis.