The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests t...

The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphoryl...

Mutations in MECP2 are the cause of Rett syndrome (RTT) in humans, a neurodevelopmental disorder that affects mainly girls. MeCP2 is a protein that binds CpG dinucleotides and is thought to act as a global transcriptional repressor. It is highly expressed in neurons, but not in glia, of the postnatal brain. The timing of MeCP2 activation correlates with the maturation of the central nervous sys...

Respiratory disturbances are a primary phenotype of the neurological disorder, Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Mouse models generated with null mutations in Mecp2 mimic respiratory abnormalities in RTT girls. Large deletions, however, are seen in only ∼10% of affected human individuals. Here we characterized respiratio...

In 1999, mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) were first reported in patients with Rett syndrome (RTT). The MECP2 gene is located at Xq28 and consists of 4 exons. About 80-90 % of the classic RTT patients harbor mutations in the coding region of MECP2, while the molecular cause is unknown in the remaining 10-20%. Several groups have searched for large rearrangemen...

PURPOSE Posterior capsular opacification (PCO) is a common long-term complication of modern cataract surgery. Remnant lens epithelial cells (LECs) undergo a myofibroblast transdifferentiation that is thought to be the initial step of PCO pathogenesis. The purpose of this study is to determine the effects of zebularine on transforming growth factor-β (TGFβ)-induced, LEC-myofibroblast transdiffer...

Aging endothelial progenitor cells (EPCs) exhibit functional impairment in terms of proliferation, migration and survival. SIRT1 plays an important role in improving EPCs function. MeCP2, another important epigenetic regulator, is involved in regulating many life-related activities such as cell growth, death and senescence. Here we aim to explore the effect of MeCP2 on the functional activities...

Rett syndrome and MECP2 duplication syndrome are neurodevelopmental disorders that arise from loss-of-function and gain-of-function alterations in methyl-CpG binding protein 2 (MeCP2) expression, respectively. Although there have been studies examining MeCP2 loss of function in animal models, there is limited information on MeCP2 overexpression in animal models. Here, we characterize a mouse li...

The discovery in 1999 that Rett syndrome (RTT) is caused by mutations in a gene encoding the methyl-CpG-binding repressor protein MECP2 provided a significant breakthrough in the understanding of this devastating disease. The subsequent production of Mecp2 knockout mice 2 years later provided an experimental resource to better understand how mutations in the MECP2 gene result in RTT. This paper...

The brain is sensitive to the dose of MeCP2 such that small fluctuations in protein quantity lead to neuropsychiatric disease. Despite the importance of MeCP2 levels to brain function, little is known about its regulation. In this study, we report eleven individuals with neuropsychiatric disease and copy-number variations spanning NUDT21, which encodes a subunit of pre-mRNA cleavage factor Im. ...