Disease relevance of Mbd1

• The defect was CD8 T cell intrinsic, because memory cell development was also delayed when MBD2(-/-) CD8 T cells were adoptively transferred into SCID mice [1].
• The role of MBD2 during the differentiation of naive CD8 T cells into effector and memory cells was determined following acute infection of MBD2-deficient mice with lymphocytic choriomeningitis virus [1].

Psychiatry related information on Mbd1

• Thus, these functional assays are useful to evaluate the consequences of mutation in the methyl-CpG-binding domain of MeCP2 and provide an insight into the relationship between the genotype and the severity of Rett syndrome [2].

High impact information on Mbd1

• A search of DNA sequence databases with the MBD sequence identified a human cDNA with potential to encode an MBD-like region [3].
• We examined cells lacking methyl CpG binding domain protein-2 (MBD2), a molecule that has been proposed to link DNA methylation to silent chromatin [4].
• Gata-3 functions, in part, to displace MBD2 from methylated DNA [4].
• Helper T cells from Mbd2(-/-) mice exhibit disordered differentiation [4].
• MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG-binding domain (MBD) only [5].

Biological context of Mbd1

• These data support the hypothesis that MBD protein-associated histone deacetylase/chromatin-remodelling complexes are recruited to the parental allele that has methylated DNA and H3-K9 methylation, and are prevented from binding to the opposite allele by H3 lysine-4 methylation [6].
• Missense mutations in the methyl-CpG-binding domain were analyzed by the transfection in mouse L929 cells and Drosophila SL2 cells [2].
• The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1 [7].
• MBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences [8].
• NMR studies have revealed that the MBD adopts a wedge-shaped molecular structure [9].

Anatomical context of Mbd1

• These data demonstrate that MBD2 is a previously unrecognized intracellular factor required for the efficient generation of protective memory CD8 T cells [1].
• Here, the functional significance of 28 MBD missense mutations identified in patients were analysed by transient expression of the mutant proteins in cultured cells [10].
• In these mice the histone deacetylase inhibitor valproate, which increases acetylated histone content in cortical GABAergic interneurons, also prevents MET-induced RELN promoter hypermethylation and reduces the methyl-CpG binding domain protein binding to RELN and GAD67 promoters [11].
• Despite its negative T15 idiotype profile, N-terminal amino acid sequencing of PCM-1 purified heavy chain and Southern blots of the hybridoma DNA indicated that it utilizes the T15 VH and JH1 genes [12].
• A synthetic RNA encoding enhanced green fluorescence protein fused to the methyl-CpG-binding domain and nuclear localization signal of human MBD1 was microinjected into metaphase II-arrested or fertilized oocytes, and the localization of methylated DNA was monitored by live cell imaging [13].

Associations of Mbd1 with chemical compounds

• The mammalian protein MBD4 contains a methyl-CpG binding domain and can enzymatically remove thymine (T) or uracil (U) from a mismatched CpG site in vitro [14].
• Within the nucleus, FADD interacted with the methyl-CpG binding domain protein 4 (MBD4), which excises thymine from GT mismatches in methylated regions of chromatin [15].
• 5-halogenated pyrimidine lesions within a CpG sequence context mimic 5-methylcytosine by enhancing the binding of the methyl-CpG-binding domain of methyl-CpG-binding protein 2 (MeCP2) [16].

Regulatory relationships of Mbd1

• We now report that in these mice, RELN and GAD67 promoters express an increased recruitment of methyl-CpG binding domain proteins [11].

Other interactions of Mbd1

• Transcriptional regulation of mouse delta-opioid receptor gene by CpG methylation: involvement of Sp3 and a methyl-CpG-binding protein, MBD2, in transcriptional repression of mouse delta-opioid receptor gene in Neuro2A cells [17].
• Chromatin immunoprecipitation analysis showed the association of a methyl-CpG-binding domain protein 2 (MBD2) with methylated mDOR promoter [18].

Analytical, diagnostic and therapeutic context of Mbd1

• Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2 [19].

References