Objectif PU.1 levels are critical for normal hematopoiesis and, even modest alterations can lead to leukemia and lymphoma. To achieve optimal expression of the PU.1 gene at different stages of hematopoiesis, multiple interactions are required between its regulatory elements to form fine chromatin architecture. While significant advances have been made in understanding which PU.1 locus chromatin states are active or silent, nothing is known how these states are propagated and maintained. The overall goal of the proposed project is to understand the role of antisense RNAs in the regulation of the PU.1 gene. Therefore I will (1) Characterize the timing, order, cellular localization, and levels of the natural noncoding antisense and coding PU.1 transcripts and formation of the active chromatin architecture within the PU.1 gene locus during cell development; (2) Investigate the functional effect of nuclear ablation of antisense concoding RNAs ablation on the formation of the active chromatin configuration and the expression of the PU.1 gene and, ultimately, on hematopoietic stem cell (HSC) fate; (3) Study the functional role of antisense noncoding RNAs in tissue culture and transgenic systems; and (4) Investigate the functional connection between the expression of the antisense noncoding RNAs and the occurrence of the other epigenetic marks, such as chromatin compaction, covalent histone modification, and DNA methylation. Accomplishment of these aims will enable us to understand the roles of antisense noncoding RNAs corresponding to PU.1 gene locus in the regulation of hematopoietic stem cell differentiation and to identify naturally occurring RNAmediated regulatory mechanisms, the manipulation of which might lead to critical changes in cell fate and provide knowledge of how changes in antisense RNAs can lead to disorders of hematopoietic stem cell function and leukemia. Champ scientifique natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicineoncologyleukemia Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Appel à propositions FP7-PEOPLE-2009-IOF Voir d’autres projets de cet appel Régime de financement MC-IOF - International Outgoing Fellowships (IOF) Coordinateur MEDIZINISCHE UNIVERSITAET WIEN Contribution de l’UE € 245 962,00 Adresse SPITALGASSE 23 1090 Wien Autriche Voir sur la carte Région Ostösterreich Wien Wien Type d’activité Higher or Secondary Education Establishments Contact administratif Ulrich Jäger (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire MEDIZINISCHE UNIVERSITAT GRAZ Participation terminée Autriche Contribution de l’UE Aucune donnée Adresse NEUE STIFTINGTALSTRASSE 6 8010 Graz Voir sur la carte Région Südösterreich Steiermark Graz Type d’activité Higher or Secondary Education Establishments Contact administratif Gerald Hoefler (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée