DNA Methylation Contributes to the Differential Expression Levels of in Male Mice Neurons and Astrocytes.

Methyl CpG binding protein-2 (MeCP2) isoforms (E1 and E2) are important epigenetic regulators in brain cells. Accordingly, MeCP2 loss- or gain-of-function mutation causes neurodevelopmental disorders, including Rett syndrome (RTT), duplication syndrome (MDS), and autism spectrum disorders (ASD). Within different types of brain cells, highest MeCP2 levels are detected in neurons and the lowest in astrocytes.

Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice.

We have previously reported the deregulatory impact of ethanol on global DNA methylation of brain-derived neural stem cells (NSC). Here, we conducted a genome-wide RNA-seq analysis in differentiating NSC exposed to different modes of ethanol exposure. RNA-seq results showed distinct gene expression patterns and canonical pathways induced by ethanol exposure and withdrawal.

Overview of the Genetic Basis and Epigenetic Mechanisms that Contribute to FASD Pathobiology.

Prenatal alcohol (ethanol) exposure (PAE) is the underlying cause for a variety of birth defects and neurodevelopmental deficits referred to as "Fetal Alcohol Spectrum Disorders (FASD)". The more visible phenotypes caused by PAE include growth retardation, and characteristic craniofacial abnormalities associated with functional and structural damage to the central nervous system. Ethanol is a teratogenic agent itself; but it can also alter gene expression.

Cellular commitment in the developing cerebellum.

The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways.

Ethanol deregulates Mecp2/MeCP2 in differentiating neural stem cells via interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2 regulatory elements.

Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms.

Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized.

Decitabine alters the expression of Mecp2 isoforms via dynamic DNA methylation at the Mecp2 regulatory elements in neural stem cells.

Background: Aberrant MeCP2 expression in brain is associated with neurodevelopmental disorders including autism. In the brain of stressed mouse and autistic human patients, reduced MeCP2 expression is correlated with Mecp2/MECP2 promoter hypermethylation. Altered expression of MeCP2 isoforms (MeCP2E1 and MeCP2E2) is associated with neurological disorders, highlighting the importance of proper regulation of both isoforms.

Dynamic expression of MEIS1 homeoprotein in E14.5 forebrain and differentiated forebrain-derived neural stem cells.

Central nervous system development is controlled by highly conserved homeoprotein transcription factors including HOX and TALE (Three Amino acid Loop Extension). TALE proteins are primarily known as HOX-cofactors and play key roles in cell proliferation, differentiation and organogenesis. MEIS1 is a TALE member with established expression in the developing central nervous system.

Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes.

Rett Syndrome (RTT) is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the relevant isoform for RTT.

Linking epigenetics to human disease and Rett syndrome: the emerging novel and challenging concepts in MeCP2 research.

Epigenetics refer to inheritable changes beyond DNA sequence that control cell identity and morphology. Epigenetics play key roles in development and cell fate commitments and highly impact the etiology of many human diseases. A well-known link between epigenetics and human disease is the X-linked MECP2 gene, mutations in which lead to the neurological disorder, Rett Syndrome.