Jan. 22, 2013 Researchers from the Centre for Genomic Research (CRG) have described the way TET2 might act in the gene regulation of myeloid leukemia. The study was carried out by transforming one blood cell (B lymphocyte) into another (a macrophage), a process called transdifferentiation.
"Learning how to induce transdifferentiation of cells with transcription factors allows us to understand the genetic instructions that defines a specialized cell type," says Eric Kallin, first author of the study.
One of the reasons for studying gene regulation through the transformation of one kind of cell into another is to maximize the changes that must occur to give rise to the resulting cellular fate. When progenitor cells are isolated and studied, a large number of specific factors are already expressed and this "primed" state can confound the full understanding of the lineage commitment process. However, using transdifferentiation (directly converting one cell into another through a technique developed by Thomas Graf, director of the CRG Gene Regulation, Stem Cells and Cancer programme and coordinator of this study), scientists can study the upregulation of fully repressed genes.
"We found that the enzyme TET2 is required to facilitate the activation of myeloid genes in our system. One hallmark of myelogenous leukemias is a block of terminal cell differentiation and the frequent mutation of TET2 that occurs in these diseases may contribute to this differentiation block," adds Kallin.
The next step is to discover how TET2 finds the genes that it activates and also how general this mechanism is in other types of cells.
The research was carried out thanks to funding from the Ministry of Science and Innovation, the AGAUR and the CONSOLIDER "Epigenética" project.
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- Eric M. Kallin, Javier Rodríguez-Ubreva, Jesper Christensen, Luisa Cimmino, Iannis Aifantis, Kristian Helin, Esteban Ballestar, Thomas Graf. Tet2 Facilitates the Derepression of Myeloid Target Genes during CEBPα-Induced Transdifferentiation of Pre-B Cells. Molecular Cell, 2012; 48 (2): 266 DOI: 10.1016/j.molcel.2012.08.007
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