Does defective binding of 5-hmC by MeCP2 contribute to Rett syndrome? | EpiBeat

DNA methylation is an epigenetic modification that plays an important role in gene expression. Aberrant changes of DNA methylation in the genome are associated with many epigenetic-related neurological disorders. However, the mechanism by which DNA methylation affects chromatin structure and gene expression is not completely understood. Methyl-CpG-binding protein 2, (MeCP2), was first identified by its affinity for DNA containing 5-methycytosine (5-mC), and mutations in MeCP2 are associated with Rett Syndrome, a disorder that results in impaired development of the nervous system.  In an article recently published in Cell, Mellen et al. discovered that in addition to 5-mC, MeCP2 also binds with high affinity to DNA containing 5-Hydroxymethycytosine (5-hmC), a more recently discovered epigenetic mark with highest levels in the brain.  Furthermore, they found that this binding facilitates gene expression through its effects on chromatin organization in cells of the cerebellum.

MECP2 duplication affects immune system as well as brain development

ScienceDaily (Dec. 5, 2012) — In 1999, Dr. Huda Zoghbi and colleagues at Baylor College of Medicine identified the genetic cause of Rett syndrome (a neurological disorder that begins after birth) -- MECP2 mutation. Too little of the MeCP2 protein associated with the gene causes the girls whom it affects to regress, gradually losing their speech, the use of their hands and many cognitive functions. MeCP2 suppressed secretion of gamma interferon from T helper cells, leading to a partial immunodeficiency.