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Mpakali A.,National and Kapodistrian University of Athens | Mpakali A.,BSRC Alexander Fleming Institute of Molecular Biology and Genetics | Kotini A.G.,National and Kapodistrian University of Athens | Kotini A.G.,BSRC Alexander Fleming Institute of Molecular Biology and Genetics | And 7 more authors.
Journal of Proteomics and Bioinformatics | Year: 2012

The 5-methyl cytosine (5meC) genomic methylation patterns play crucial roles in mammalian development and are altered in cancer. The enzymes that create, maintain and modify the DNA methylation patterns are the DNA methyltransferases (Dnmts) which are all encoded by essential genes. The de novo Dnmts -Dnmt3a and Dnmt3b-establish the DNA methylation patterns early in mammalian development by introducing DNA methylation marks where no previous methylation exists. These enzymes do not exhibit affinity for specific DNA sequences, thus their recruitment to specifc DNA loci and their activities must be tightly regulated. In particular, Dnmt3a2 -one of the two protein isoforms produced by the Dnmt3a locus- is the most abundant DNA methyltransferase in mouse Embryonic Stem Cells. To identify Dnmt3a (and DNA methylation) regulators we have searched for Dnmt3a2 interacting proteins in mESCs by pull down and Mass Spectrometry. The DEAD box p68/Ddx5 RNA helicase was identified to directly interact with Dnmt3a1 and Dnmt3a2 in vitro and in vivo. We have created a mutant Ddx5 (Dd×5 MUT) protein exhibiting an altered nuclear localization pattern compared to the wt protein. Both wt and mutant Ddx5 interact directly in vitro and co localize in vivo with Dnmt3a proteins. Our data suggest that the Dnmt3a/Ddx5 interaction might be significant for modulating the DNA methylation/demethylation dynamics in vivo. © 2012 Mpakali A, et al. Source

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