geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Methyl-CpG binding domain proteins and their involvement in the regulation of the MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 gene promoters


, : Methyl-CpG binding domain proteins and their involvement in the regulation of the MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 gene promoters. Molecular Cancer Research 5(7): 749-759

Promoter hypermethylation is responsible for the restricted expression of the tumor-associated MAGE antigens. In order to elucidate the mechanism underlying methylation-dependent repression, we examined the involvement of methyl-CpG binding proteins, MBD1, MBD2a, and MeCP2, in silencing of MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 genes. Electrophoretic mobility shift assays displayed binding of MBD1 to the methylated and unmethylated MAGE-A promoters. Using chromatin immunoprecipitation assays, in vivo binding of MBD1 and MeCP2 to the promoters could be observed in MCF-7 and T47D cells. Transient transfection assays of MCF-7 cells were done with the transcriptional repression domains (TRD) of MBD1, MBD2a, and MeCP2, and MAGE-A1, MAGE-A2, MAGE-A3, and MAGE-A12 promoters. Whereas the TRD of MBD1 and MeCP2 repressed the MAGE-A promoters, the TRD of MBD2 had no inhibiting effect on the promoter activity. Furthermore, cotransfections of Mbd1-deficient mouse fibroblasts and MCF-7 cells with MBD2a, MeCP2, and the MBD1 splice variants, 1v1 and 1v3, showed that strong methylation-dependent repression of the MAGE-A promoters could not be further down-regulated by these proteins. However, the two MBD1 splice variants, 1v1 and 1v3, were able to repress the basal activity of unmethylated MAGE-A promoters. Additional cotransfection experiments with both isoforms of MBD1 and the transcription factor Ets-1 showed that Ets-1 could not abrogate the MBD1-mediated suppression. In contrast with the repressive effect mediated by MBD1, MBD2a was found to up-regulate the basal activity of the promoters. In conclusion, these data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes.

US$19.90

PMID: 17634428

DOI: 10.1158/1541-7786.MCR-06-0364


Other references

Michalska Krzanowska, Grazyna, 1995: Comparative studies of rhombencephalon vascularization in rabbit and man in the light of anatomic and microangiographic studies. A comparative study of a microvascularization of the rhombencephalon, especially pre- and capillary system, in rabbits and in humans was performed. It was intended to find out whether there were any similarities and differences in rhombencephalon...

Smith, E.; Ryall, N., 2010: Residual limb osteomyelitis: a case series from a national prosthetic centre. To examine the impact of residual limb osteomyelitis (RLO) on the rehabilitation of lower limb amputees. Retrospective review of the case notes of patients with RLO. Information sought included details of amputation, clinical features of investiga...

Felle, H.H.; Kondorosi, E.; Kondorosi, A.; Schultze, M., 2000: How alfalfa root hairs discriminate between Nod factors and oligochitin elicitors. Using ion-selective microelectrodes, the problem of how signals coming from symbiotic partners or from potential microbial intruders are distinguished was investigated on root hairs of alfalfa (Medicago sativa). The Nod factor, NodRm-IV(C16:2,S),...

Castrillo, L.A.; Wiegmann, B.M.; Brooks, W.M., 1999: Genetic variation in Beauveria bassiana populations associated with the darkling beetle, Alphitobius diaperinus. A study was conducted to assess genetic variation within and among populations of Beauveria bassiana (Deuteromycotina: Hyphomycetes) associated with the darkling beetle, Alphitobius diaperinus (Coleoptera: Tenebrionidae), using RAPD markers. A hie...

Hong, C-Soo.; Park, B-Yong.; Saint-Jeannet, J-Pierre., 2008: Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm. Two independent signals are necessary for neural crest (NC) induction in Xenopus: a Bmp signal, which must be partially attenuated by Bmp antagonists, and a separate signal mediated by either a canonical Wnt or an Fgf. The mesoderm underlying the...

Hwang, J.H.; Larson, R.K.; Abu-Omar, M.M., 2003: Kinetics and mechanistic studies of anticarcinogenic bisperoxovanadium(V) compounds: ligand substitution reactions at physiological pH and relevance to DNA interactions. Bisperoxovanadium(V) compounds with bidentate ligands have shown tumor growth inhibition by cleaving DNA. The kinetics and mechanisms of ligand substitution reactions of two bisperoxovanadium(V) compounds [VO(O(2))(2)(bpy)](-) (bpVbpy) and [VO(O(2...

Araujo, E.; Matson, E., 1987: Copper-aluminum alloys. Casting contraction of various copper-aluminum system alloys. Rgo 35(3): 222-224

Rapenne, F., 1981: Controle genetique de la differenciation et du metabolisme des organes de Zenker (cellule a acide urique) chez, Asellus aquaticus Linne (crustaces, isopodes). Mise en evidence d'un relation entre la regression partielle de la pigmentation (panachure) et la regression partielle de ces organes. Comptes Rendus de l'Academie des Sciences Serie III Sciences de la Vie, 2929: 589-593

Gonçalves, T.Siqueira.; Morganti, Mário.A.; Campos, Lís.C.; Rizzatto, S.M.D.; Menezes, L.M., 2006: Allergy to auto-polymerized acrylic resin in an orthodontic patient. This article reports on a 60-year-old woman who had an allergic reaction to methylmethacrylate self-curing acrylic resin during orthodontic treatment. A localized hypersensitive reaction appeared on the palate after an orthodontic retainer was pla...

Liu, Z.; Yang, C-Wen.; Xu, Y-Chun.; Jin, Z-Min.; Ma, J-Zhang., 2015: Application of genetic diversity in the researches on rodents. Genetic diversity is the base of the species diversity and ecosystem diversity, and also the foundation for biological evolution and species differentiation. Furthermore, genetic diversity is important evidence for evaluation of biological resourc...