Multifaceted Roles of MeCP2 in Cellular Regulation and Phase Separation: Implications for Neurodevelopmental Disorders, Depression, and Oxidative Stress.

Methyl CpG binding protein 2 (MeCP2) is a chromatin-associated protein that remains enigmatic despite more than 30 years of research, primarily due to the ever-growing list of its molecular functions, and, consequently, its related pathologies. Loss of function MECP2 mutations cause the neurodevelopmental disorder Rett syndrome (RTT); in addition, dysregulation of MeCP2 expression and/or function are involved in numerous other pathologies, but the mechanisms of MeCP2 regulation are unclear. Advancing technologies and burgeoning mechanistic theories assist our understanding of the complexity of MeCP2 but may inadvertently cloud it if not rigorously tested.

Microplastics and PFAS air-water interaction and deposition.

Although microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) have received tremendous attention separately, understanding their ubiquitous presence in the environment, persistence and toxicity requires comprehensive study of the fate and transport of co-existing MPs and PFAS. MPs may have large sorption capacity and can serve as vectors for PFAS to undergo long-range transport in water. Atmospheric deposition of both PFAS and MPs has been reported in urban, rural, and remote areas.

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.