Lipides, Nutrition, Cancer

Séminaires LNC Année 2013

Dr Fabien Guidez

U940 Inserm ; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Université Paris 7, Paris

Mardi 2 Avril 2013 à 14h30

Salle Klepping (faculté de médecine et de Pharmacie- 3ème étage)

"Novel Dual Regulation of L1 retrotransposon by PLZF"

Regulation of cell-specific patterns by epigenetic mechanisms is critical and has been associated with the organization of DNA methylation regions (DMR) in order to regulate stem cell homeostasis and genome protection. We developed two mouse models of PLZF acetylation mutants and identified differentially DNA methylation regions (DMR). PLZF-associated DMRs, contain repeat elements including non-LTR (LINE, SINE/Alu) and LTR (ERV and MaLR) transposons. PLZF binds specifically these repeats through a conserved DNA binding site and induces repression of the active retrotransposons by specifically targeting HDAC and DNMT activities but also initiate the formation of insulator-like boundaries interacting with truncated LINE sequences often located in intronic coding sequences. We wish to investigate more closely the implications of the PLZF-LINE interaction and its implication in the maintenance and safeguarding of adult progenitors and pursue the characterization of other identified DMRs to understand PLZF-associated DMRs implication in genome regulation, both at the transcriptional, chromatin organization and genome integrity levels.

Retinoblastoma protein and the leukemia-associated PLZF transcription factor interact to repress target gene promoters.
Petrie K, Guidez F, Zhu J, Howell L, Owen G, Chew YP, Parks S, Waxman S, Licht J, Mittnacht S, Zelent A. Oncogene. 2008 Sep 4;27(39):5260-6

RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
Guidez F, Parks S, Wong H, Jovanovic JV, Mays A, Gilkes AF, Mills KI, Guillemin MC, Hobbs RM, Pandolfi PP, de Thé H, Solomon E, Grimwade D.
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18694-9.

Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein.
Guidez F, Howell L, Isalan M, Cebrat M, Alani RM, Ivins S, Hormaeche I, McConnell MJ, Pierce S, Cole PA, Licht J, Zelent A.
Mol Cell Biol. 2005 Jul;25(13):5552-66.

Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.
Guidez F, Petrie K, Ford AM, Lu H, Bennett CA, MacGregor A, Hannemann J, Ito Y, Ghysdael J, Greaves M, Wiedemann LM, Zelent A.
Blood. 2000 Oct 1;96(7):2557-61.

Invitation: Laurent Delva UMR866

Le séminaire aura lieu à la Faculté de Médecine Dijon

Renseignements - omicheau@u-bourgogne.fr Tel: 03 80 39 34 68.