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Characterization of microRNAs role in regulating epigenetic machenary in human tumor cells

Grant number: 13/05583-4
Support type:Regular Research Grants
Duration: July 01, 2013 - December 31, 2015
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Lygia da Veiga Pereira
Grantee:Lygia da Veiga Pereira
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Luciana dos Reis Vasques

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 preimplantational period. This phenomenon initiates a range of changes in 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 DNA methylation establishment in embryos, 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, is goal of this study to characterize the regulation of DNMT3B gene by microRNAs in human tumor cells. Additionally, this project will provide new tools to functional study of microRNAs and DNA global methylation in our laboratory. (AU)