Validation of microRNAs candidate for the regulation of DNA methyltransferase 3B (DNMT3B) expression

• Grant number: 12/07199-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2012
• Effective date (End): January 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luciana dos Reis Vasques
• Grantee: Cláudia Regina Gasque Schoof
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

DNA methylation is a well-known epigenetic modification and it is established in the early mammalian embryonic development, concomitant with the process of differentiation, which occurs in the preimplantation period. This fennomenon initiates a range of changes in the chromatin, being one of the main agents of gene regulation in early development.Among the proteins belonging to the DNA metiltransferases family, Dnmt3a and Dnmt3b have the ability to establish de novo DNA methylation found at this stage of development, methylating CpG dinucleotides. Despite having overlapping function, the former is more involved with the methylation of individual genetic loci that undergo genomic imprinting, while the latter is involved with methylation of CG-rich regions, such as satellite repeats. After global methylation is established in the embryo, the epigenetic machinery is downregulated, including Dnmt3b. Atypical changes in global DNA methylation, as well as CpG Islands, are found in most tumors, in which aberrant DNMTs expression takes place. Little is known about how the expression of their genes is regulated, both in tumor cells and in early development. Thus, microRNAs, small RNA molecules with post-transcriptional regulatory function, have been associated with this process. Considering that many microRNAs have been predicted to targeted DNMT3b/ Dmnt3b mRNA, is goal of this study to identify new candidates for targeting DNMT3B/Dnmt3b mRNA in tumor cells.