congresos y reuniones científicas
Role of ASH2L and NCOA6 in glucocorticoid-mediated apoptosis in leukemic cells.
SILBERMINS, M.; PECCI, A.; ROCHA VIEGAS, L.
Congreso; XII PABMB Congress.; 2013
Glucocorticoids are frequently used in the treatment of hematopoietic diseases due to its pro-apoptotic properties, representing an alternative and promising therapy in leukemia. We have already observed that leukemic U937 cells undergo apoptosis after dexametasone (Dex) treatment and this effect correlates with the down-regulation of the anti-apoptotic isoform Bcl-XL. Moreover, ASH2L (H3K4 methylase activity) and NCOA6 (steroid receptor co-activator) showed to be necessary for programmed cell death in response to Dex. The main goal of this project is to study the role of ASH2L and NCOA6 proteins as putative epigenetic modulators on glucocorticoid-mediated apoptosis in human leukemic cells. Here we show that no down-regulation of bcl-XL mRNA is observed when ASH2L or NCOA6 are silenced. We observed that the glucocorticoid receptor (GR) and ASH2L co-immunoprecipitate in the presence of Dex in wt cells, but this endogenous interaction is lost when NCOA6 expression is silenced. We also evaluated the recruitment of GR to hormone-response elements located in the intron of bcl-X gene (+18, +42, +58 kb from TSS). Interestingly, GR is already recruited to chromatin in the absence of hormone (0,6-0,8% input), and when Dex is added the receptor is displaced (0,2% input) EN LOS TRES SITIOS?. In conclusion, our results suggest a concerted epigenetic mechanism for transcriptional regulation during glucocorticoid-mediated apoptosis in leukemia. Funding acknowledgements UBACYT IJ 2011-2013 and PIP Joven 2012-2014