Ask about this productRelated genes to: MBD3 Blocking Peptide
- Gene:
- MBD3 NIH gene
- Name:
- methyl-CpG binding domain protein 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19p13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-11
- Date modifiied:
- 2014-11-19
- Gene:
- MBD3L1 NIH gene
- Name:
- methyl-CpG binding domain protein 3 like 1
- Previous symbol:
- MBD3L
- Synonyms:
- -
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-21
- Date modifiied:
- 2016-03-15
Related products to: MBD3 Blocking Peptide
Related articles to: MBD3 Blocking Peptide
- The methyl-cytosine binding domain 2 (MBD2)-nucleosome remodeling and deacetylase (NuRD) complex recognizes methylated DNA and silences expression of associated genes through histone deacetylase and nucleosome remodeling functions. Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66α) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2β) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai, M. A., Walavalkar, N. M., Wang, S. Z., Zu Zhu, S., Ginder, G. D., and Williams, D. C., Jr. (2011) p66α-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc. Natl. Acad. Sci. U.S.A. 108, 7487-7492). The p66α-MBD2 interaction differs from most coiled-coils studied to date by forming an anti-parallel heterodimeric complex between two peptides that are largely monomeric in isolation. To further characterize unique features of this complex that drive heterodimeric specificity and high affinity binding, we carried out biophysical analyses of MBD2 and the related homologues MBD3, MBD3-like protein 1 (MBD3L1), and MBD3-like protein 2 (MBD3L2) as well as specific mutations that modify charge-charge interactions and helical propensity of the coiled-coil domains. Analytical ultracentrifugation analyses show that the individual peptides remain monomeric in isolation even at 300 μM in concentration for MBD2. Circular dichroism analyses demonstrate a direct correlation between helical content of the coiled-coil domains in isolation and binding affinity for p66α. Furthermore, complementary electrostatic surface potentials and inherent helical content of each peptide are necessary to maintain high-affinity association. These factors lead to a binding affinity hierarchy of p66α for the different MBD2 homologues (MBD2 ≈ MBD3 > MBD3L1 ≈ MBD3L2) and suggest a hierarchical regulatory model in tissue and life cycle stage-specific silencing by NuRD complexes. - Source: PubMed
Publication date: 2012/12/13
Walavalkar Ninad MGordon NathanielWilliams David C - Genome-wide erasure of CpG methylation occurs along the paternal pronucleus in fertilized oocytes. This process involves an active, replication-independent enzymatic step, which has remained enigmatic. MBD3L1 and MBD3L2 are two mammalian homologues of the methyl-CpG-binding protein genes MBD2 and MBD3 that arose from recent gene duplication events. Expression of Mbd3l1 occurs specifically in haploid male germ cells. Mbd3l2 expression is restricted to metaphase II oocytes and zygotes making both proteins candidates for the zygotic demethylation process. Neither of these genes was able to promote reactivation of a methylation-silenced reporter gene. We created Mbd3l1 and Mbd3l2 knockout mice, which were viable and fertile. We show that demethylation of the paternal pronucleus in Mbd3l1-/- and Mbd3l2-/- mice is identical to that in wild-type controls. These data suggest that Mbd3l1 and Mbd3l2 are not involved in genome-wide demethylation of paternal genomes in mouse zygotes and are dispensable for normal development. - Source: PubMed
Jin Seung-GiTsark WalterSzabó Piroska EPfeifer Gerd P - MBD2 and MBD3 are two proteins that contain methyl-CpG binding domains and have a transcriptional repression function. Both proteins are components of a large CpG-methylated DNA binding complex named MeCP1, which consists of the nucleosome remodeling and histone deacetylase complex Mi2-NuRD and MBD2. MBD3L2 (methyl-CpG-binding protein 3-like 2) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG-binding domain. Unlike MBD3L1, which is specifically expressed in haploid male germ cells, MBD3L2 expression is more widespread. MBD3L2 interacts with MBD3 in vitro and in vivo, co-localizes with MBD3 but not MBD2, and does not localize to methyl-CpG-rich regions in the nucleus. In glutathione S-transferase pull-down assays, MBD3L2 is found associated with several known components of the Mi2-NuRD complex, including HDAC1, HDAC2, MTA1, MBD3, p66, RbAp46, and RbAp48. Gel shift experiments with nuclear extracts and a CpG-methylated DNA probe indicate that recombinant MBD3L2 can displace a form of the MeCP1 complex from methylated DNA. MBD3L2 acts as a transcriptional repressor when tethered to a GAL4-DNA binding domain. Repression by GAL4-MBD3L2 is relieved by MBD2 and vice versa, and repression by MBD2 from a methylated promoter is relieved by MBD3L2. The data are consistent with a role of MBD3L2 as a transcriptional modulator that can interchange with MBD2 as an MBD3-interacting component of the NuRD complex. Thus, MBD3L2 has the potential to recruit the MeCP1 complex away from methylated DNA and reactivate transcription. - Source: PubMed
Publication date: 2005/01/27
Jin Seung-GiJiang Chun-LingRauch TiborLi HongweiPfeifer Gerd P - Methyl-CpG-binding domain proteins 2 and 3 (MBD2 and MBD3) are transcriptional repressors that contain methyl-CpG binding domains and are components of a CpG-methylated DNA binding complex named MeCP1. Methyl-CpG-binding protein 3-like 1 (MBD3L1) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG binding domain. MBD3L1 interacts with MBD2 and MBD3 in vitro and in yeast two-hybrid assays. Gel shift experiments with a CpG-methylated DNA probe indicate that recombinant MBD3L1 can supershift an MBD2-methylated DNA complex. In vivo, MBD3L1 associates with and colocalizes with MBD2 but not with MBD3 and is recruited to 5-methylcytosine-rich pericentromeric heterochromatin in mouse cells. In glutathione S-transferase pull-down assays MBD3L1 is found associated with several known components of the MeCP1.NuRD complex, including HDAC1, HDAC2, MTA2, MBD2, RbAp46, and RbAp48, but MBD3 is not found in the MBD3L1-bound fraction. MBD3L1 enhances transcriptional repression of methylated DNA by MBD2. The data are consistent with a role of MBD3L1 as a methylation-dependent transcriptional repressor that may interchange with MBD3 as an MBD2-interacting component of the NuRD complex. MBD3L1 knockout mice were created and were found to be viable and fertile, indicating that MBD3L1 may not be essential or there is functional redundancy (through MBD3) in this pathway. Overall, this study reveals additional complexities in the mechanisms of transcriptional repression by the MBD family proteins. - Source: PubMed
Publication date: 2004/09/28
Jiang Chun-LingJin Seung-GiPfeifer Gerd P - Methylation of cytosines at CpG dinucleotides is essential for mammalian development. MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of proteins that contain a methyl-CpG binding domain (MBD). Except for MBD4, these proteins are involved in gene silencing imposed by methylated DNA. We have identified a human gene that codes for a protein that is 42% identical to MBD3 and 38% identical to MBD2 but lacks the methyl-CpG binding domain. The recombinant protein does not bind to methylated DNA in vitro. The corresponding mouse Mbd3L1 gene was also cloned. The MBD3L1 gene is expressed specifically in testis. During spermatogenesis, expression of MBD3L1 is observed only in round spermatids, suggesting a role for the gene product in the postmeiotic stages of male germ cell development. The MBD3L1 protein is localized to discrete areas in the nucleus and contains an N-terminal transcriptional repression domain. This repression is independent of histone deacetylase inhibition. A homologue of MBD3L1, MBD3L2, was also identified and cloned. Expression of MBD3L2 was found in germ cell tumors and some somatic tissues. These novel proteins may function as counterparts of MBD2 and/or MBD3 in developmental stage-specific transcriptional repression. - Source: PubMed
Jiang Chun LingJin Seung GiLee Dong HyunLan Zi JianXu XuepingO'Connor Timothy RSzabó Piroska EMann Jeffrey RCooney Austin JPfeifer Gerd P