Abstracts (poster) - Wissenschaft Online

Christine Champion, Loïc Ponger, Catherine Senamaud-Beaufort, Dominique
Guianvarc'h, Ludovic Halby, Anne-Laure Guieysse-Peugeot, Paola B. Arimondo
Biochemical approaches to study the DNA methylation
mechanisms involved in tumorigenesis
Cancer cells show a highly disturbed epigenetic landscape, with a global
hypomethylation of the genome that induces abnormal expression of genes (such as
oncogenes) and a local hypermethylation of promotors that silences tumor suppressor
genes (TSG). DNA methylation is catalysed by a family of enzymes called DNA
methyltransferases (DNMTs) and only occurs at position 5 of cytosines in CpG
dinucleotides (in Vertebrates) that are not randomly distributed in the genome but
mainly grouped in CpG islands. Yet the mechanism by which specific de novo
methylation is directed to the TSG promotors remains still unknown. Indeed, it would be
of great therapeutic interest to block this specific hypermethylation of TSG promotors in
order to restore in malignant cells their natural ability to block tumorigenesis.
We have chosen to focus on prostate cancer and two TSG for which inactivation is due to
promotor hypermethylation : RASSF1A and RARβ2.
On one hand, we investigate whether short DNA sequences influence the DNA
methylation pattern. By a bioinformatic analysis we have found 10 DNA motifs that are
overrepresented in hypermethylated promotors in prostate cancer versus non
hypermethylated promotors.
On the other hand, we are developing two affinity chromatography approaches to
identify the protein partners of DNMTs involved in DNA methylation.
contact:
PhD Student Christine Champion
Museum National d'Histoire Naturelle
MNHN USM 503, CNRS UMR5153, INSERM U565
christine.champion@mnhn.fr
43, rue Cuvier
75231 Paris cedex 5 (France)
additional information
Dominique Guianvarc'h : CNRS UMR7613-Université Paris VI