MeCP2: the long trip from a chromatin protein to neurological disorders

• The intrinsically disordered protein nature of MeCP2 is critical for its manifold interactions and functions.
• MeCP2 is an extremely abundant chromosomal protein in neurons.
• In addition to Rett syndrome, MeCP2 is involved in other neurological disorders.
• MeCP2 activity is regulated by many post-translational modifications (PTMs).

Since the discovery of its fundamental involvement in Rett syndrome, methyl CpG binding protein 2 (MeCP2) has been the focus of an exhaustive biochemical and functional characterization. It is now becoming apparent that the intrinsic highly disordered nature of MeCP2, which is amenable to a plethora of post-translational modifications (PTMs), allows it to recognize a large number of protein interacting partners, including histones. MeCP2 is highly abundant in the brain and it is an important component of neuronal chromatin; nevertheless, the organization and implications of its involvement in terms of DNA methylation binding dependence and effects on transcription are still not well understood. Recent results have shown that MeCP2 plays an important role in brain development, aging, and in neurological disorders.