How does MeCP2 regulate gene expression?
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Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as well as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expression regulation.
How do you identify a promoter methylation?
Currently, there are three primary methods to identify and quantify DNA methylation. These are: sodium bisulfite conversion and sequencing, differential enzymatic cleavage of DNA, and affinity capture of methylated DNA (1). Restriction enzyme based differential cleavage of methylated DNA is locus-specific.
How does MeCP2 repress transcription?
Recently we uncovered evidence that MeCP2 controls transcription of very long genes with critical neuronal functions by binding a unique form of DNA methylation, enriched in neurons. Here, we provide evidence that MeCP2 represses transcription by binding within transcribed regions of genes.
How does MeCP2 modify chromatin?
Indeed, in vitro and in vivo, MeCP2 associates with an H3-Lys9 histone methyltransferase activity, that promotes the methylation of Lys9 of histone H3 on a DNA-methylated target gene, thus reinforcing the repressive chromatin state .
What is the role of MECP2?
Normal Function The MECP2 gene provides instructions for making a protein called MeCP2. This protein helps regulate gene activity (expression) by modifying chromatin, the complex of DNA and protein that packages DNA into chromosomes.
Where is the MECP2 gene expressed?
MECP2 encodes for methyl-CpG-binding protein 2 (MeCP2), a chromatin binding protein (11) that is expressed ubiquitously in the body with major expression in the central nervous system (CNS).
How can you Analyse for methylation in a gene?
Southern-blot hybridization for DNA methylation analysis is based on DNA digestion by a methylation-sensitive restriction enzyme and subsequent hybridization using a probe for a specific genomic region. Bisulfite-converted DNA is amplified by PCR using primers located in genomic regions lacking CpG sites.
What is methylation analysis?
Methylation analysis is the study of chromosomal patterns of DNA or histone modification by methyl groups. The cytosine (C) base in DNA and lysine residue in histone tails can be methylated.
How does MeCP2 link DNA and histone modifications?
The recruitment of MeCP2 to methylated CpG dinucleotides represents a major mechanism by which DNA methylation can repress transcription. MeCP2 silences gene expression partly by recruiting histone deacetylase (HDAC) activity, resulting in chromatin remodeling.
What do histone deacetylases do?
Histone deacetylase (HDAC) is an enzyme that removes the acetyl group from histone proteins on DNA, making the DNA less accessible to transcription factors.
Which chromosome is MECP2 on?
The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 (“Xq28”), from base pair 152,808,110 to base pair 152,878,611. MECP2 is an important reader of DNA methylation. Its methyl-CpG-binding (MBD) domain recognizes and binds 5-mC regions. MECP2 is X-linked and subject to X inactivation.
How does MECP2 mutation cause Rett syndrome?
MeCP2 Mutations and the High Complexity of MeCP2 Stability. Rett syndrome can arise from a number of missense, nonsense, frame shift, splice site, and start codon mutations as well as larger deletions that can lead to a range of phenotypes with varying degrees of severity (Chahrour and Zoghbi, 2007).