Emerging physiological and pathological roles of MeCP2 in non-neurological systems

Abstract

Numerous neurological and non-neurological disorders are associated with dysfunction of epigenetic modulators, and methyl CpG binding protein 2 (MeCP2) is one of such proteins. Initially identified as a transcriptional repressor, MeCP2 specifically binds to methylated DNA, and mutations of MeCP2 have been shown to cause Rett syndrome (RTT), a severe neurological disorder. Recently, accumulating evidence suggests that ubiquitously expressed MeCP2 also plays a central role in non-neurological disorders including cardiac dysfunction, liver injury, respiratory disorders, urological dysfunction, adipose tissue metabolism disorders, movement abnormality and inflammatory responses in a DNA methylation dependent or independent manner. Despite significant progresses in our understanding of MeCP2 over the last few decades, there is still a considerable knowledge gap to translate the in vitro and in vivo experimental findings into therapeutic interventions. In this review, we provide a synopsis of the role of MeCP2 in the pathophysiology of non-neurological disorders, MeCP2-based research directions and therapeutic strategies for non-neurological disorders are also discussed.

Keywords: DNA methylation; Epigenetics; MeCP2; Non-neurological disorders; Rett syndrome.