"http://www.isvav.cz/projectDetail.do?rowId=IAA500040802"^^ . . "A new mechanism of acute promyelocytic leukemia pathogenesis was identified. Onkoprotein PML/RARa binds to RARE elements in Alu repeat clusters and induces formation of chromatin loops that deliver PML/RARa to specif. gene clusters and thus silence them."@en . "6"^^ . . . "2008-01-01+01:00"^^ . "1"^^ . . " higher-order chromatin structure" . "0"^^ . "0"^^ . . . . . "2013-06-28+02:00"^^ . . " PML/RARa fusion oncoprotein" . . . "New mechanisms of oncoprotein action in genesis of promyelocytic leukemia"@en . . "Nov\u00E9 mechanismy aktivit onkoprotein\u016F ve vzniku promyelocytick\u00E9 leuk\u00E9mie" . "The scope of project is to contribute to our understanding to mechanisms of gene deregulation in acute promyelocytic leukemia (APL), which would help to identify new targets for specific therapy. Our existing results (Dellino et al., submitted to Nature) indicate that not only direct binding of the PML/RARa oncoprotein to RARE elements in promoters of down-regulated genes is responsible for gene silencing in APL. Instead, a significant proportion of genes is silenced by an indirect mechanism, involving changes in higher-order chromatin structure provoked by PML/RARa. This behavior is atypical and was not described for any other oncoprotein. Employing the microchip technology, RT-PCR, 3D-FISH, ImmunoFISH, Chromatin Capture Conformation Assay (3C) and ImmunoChip in combination with high-resolution confocal microscopy, we would like to further study %22indirect%22 mechanisms of carcinogenesis induced by PML/RARa and characterize effects of the most efficient anti-PML drugs to this process."@en . "IAA500040802" . . . "2011-12-31+01:00"^^ . . . "Acute promyelocytic leukemia; PML/RARa fusion oncoprotein; higher-order chromatin structure, carcinogenesis; gene silencing"@en . "2011-03-18+01:00"^^ . . . "Byl odhalen nov\u00FD mechanismus patogeneze akutn\u00ED promyelocyt\u00E1rn\u00ED leuk\u00E9mie. Vazba onkoproteinu PMLR/RARa na RARE elementy klastr\u016F repetic Alu vyvol\u00E1v\u00E1 tvorbu chromatin. smy\u010Dek, kter\u00E9 odtud \u201Edopravuj\u00ED\u201C PML/RARa na specifick\u00E9 klastry gen\u016F a t\u00EDm je utlumuj\u00ED."@cs . "C\u00EDlem projektu je p\u0159isp\u011Bt k porozum\u011Bn\u00ED mechanism\u016Fm deregulace genov\u00E9 exprese u akutn\u00ED promyelocyt\u00E1rn\u00ED leuk\u00E9mie (APL), co\u017E by m\u011Blo napomoci identafikaci nov\u00FDch %22ter\u010D\u016F%22 pro c\u00EDlenou a efektivn\u00ED terapii. Na\u0161e dosavadn\u00ED v\u00FDsledky (Dellino et al., 2007, postoupeno do \u010Dasopisu Nature)ukazuj\u00ED, \u017Ee na deregulaci gen\u016F u APL se, krom\u011B p\u0159\u00EDm\u00E9 vazby f\u00FAzn\u00EDho onkoproteinu PML/RARa na RARE elementy v promotorech posti\u017Een\u00FDch gen\u016F, pod\u00EDl\u00ED tak\u00E9 mechanismy nep\u0159\u00EDm\u00E9, zahrnuj\u00EDc\u00ED zm\u011Bny struktury chromatinu vy\u0161\u0161\u00EDho \u0159\u00E1du vyvolan\u00E9 proteinem PML/RARa. Toto n\u00E1mi odhalen\u00E9 chov\u00E1n\u00ED PML/RARa je velmi netypick\u00E9, a nebylo doposud pops\u00E1no ani pro \u017E\u00E1dn\u00FD jin\u00FD onkoprotein. S vyu\u017Eit\u00EDm metod mikro\u010Dipov\u00E9 technologie, RT-PCR, 3D-FISH, Immuno-FISH, Chromatin Conformation Capture assay (3C) a ImmunoChip v kombinaci s konfok\u00E1ln\u00ED mikroskopi\u00ED o vysok\u00E9m rozli\u0161en\u00ED bychom proto cht\u011Bli d\u00E1le studovat nep\u0159\u00EDm\u00E9 mechanismy karcinogeneze vyvolan\u00E9 proteinem PML/RAR a charakterizovat efekt v dne\u0161n\u00ED dob\u011B nej\u00FA\u010Dinn\u011Bj\u0161\u00EDch anti-APL l\u00E9k\u016F na tento proces" . "Acute promyelocytic leukemia" . " carcinogenesis" . "6"^^ .