Disease relevance of Mecp2

• Reduction of MeCP2 protein expression may influence the initiation and/or progression of hepatic cancer induced by methyl deficiency and may provide a useful marker of pre-neoplastic change [1].
• A chromatin immunoprecipitation assay demonstrated that MeCP2 was associated with the MT-I promoter in the hepatoma implicating its involvement in repressing the methylated promoter [2].

Psychiatry related information on Mecp2

• Rett syndrome (RS) is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) and is characterized by arrested postnatal neurodevelopment [3].

High impact information on Mecp2

• In extracts from rodent tissues, cultured cells, and Xenopus laevis oocytes, we find that only a small amount of mammalian MeCP2 interacts with Sin3a and that this interaction is not stable [4].
• We propose that genome-wide and/or -specific local DNA methylation may be maintained by the Dnmt1-MeCP2 complexes, bound to hemimethylated DNA [5].
• Here we show that the methyl-CpG binding protein, MeCP2, interacts directly with the maintenance DNA methyltransferase, Dnmt1 [5].
• Our data highlight GABAergic neurons as major target cells expressing Mecp2 in response to the serotonin-elevating agents and suggest that serotonin signaling enhances gene silencing in postmitotic neurons [6].
• Using immunohistochemistry, we found that Mecp2, as well as the methyl-CpG-binding protein MBD1, were significantly induced in normal adult rat brain after repeated injections of fluoxetine or cocaine for 10 days (one injection per day) [6].

Biological context of Mecp2

• Moreover, a known gene target of MeCP2, the tumor suppressor gene metallothionein-I, was over-expressed in the deficient rat livers at both 9 and 36 weeks, suggesting that reduction in MeCP2 may have functional consequences [1].
• This increase was associated with differentiation, as MeCP2 expression levels did not vary within different phases of the cell cycle [7].
• Further support for a correlation of MeCP2 expression with cell differentiation was observed in culture, where Western blot analysis during the in vitro differentiation of PC12, NG108-15, and SH-SY5Y cells revealed that MeCP2 levels increased as the cells acquired a more differentiated phenotype [7].
• We have investigated the gene expression responses of a family of methyl CpG-binding domain-containing factors (MeCP2, MBD1, MBD2, and MBD3) in the hippocampus of electrically kindled rats [8].

Anatomical context of Mecp2

• Although more subtle, the degree of MeCP2 expression in cortex and hippocampus was most closely correlated with synaptogenesis in both regions [9].
• The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells [7].
• At the protein level, MeCP2 was strongly expressed in adult forebrain neurons, but was not detected in astrocytes [7].
• For example, the early-generated Purkinje cells became MeCP2 positive by P6, while the late-generated granule cells did not express MeCP2 until the fourth postnatal week [9].
• The nonubiquitous expression of MeCP2 was also observed in the embryonic cortex, as about one-third of acutely dissociated embryonic day 14 neuroepithelial cells failed to stain with MeCP2 [7].

Associations of Mecp2 with chemical compounds

• Mecp2 was not induced by repeated injections of 1-(2-bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine (GBR-12909) or nortriptyline [6].
• Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver [1].

Other interactions of Mecp2

• Except in the olfactive nuclei, very few cells showed detectable MeCP2 protein at birth [3].
• Although strong MeCP2 expression was detected in approximately 75% of beta-III tubulin-positive cells, only about 25% of nestin-positive precursor cells were MeCP2 positive [7].
• In addition, a marked inhibition of neurite extension and proper localization of a marker for synapse formation, synapsin I, were observed when MeCP2 expression was decreased by the addition of an antisense morpholino oligomer directed to the translational initiation site for MeCP2beta [10].

Analytical, diagnostic and therapeutic context of Mecp2

• By measuring the amount of protein using the Western blot technique, or by determining the percentage of immunoreactive cells, significant heterogeneity in MeCP2 distribution among various brain areas was observed [3].
• At 3, 6 and 12 h following reperfusion, MeCP2 and MBD1 expression is maintained at control levels throughout the hippocampus [11].

References