IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of UTX in RAR-mediated gene regulation in leukemia
Autor/es:
LUCIANA ROCHA VIEGAS; R. VILLA; A. GUTIERREZ; O. IRIONDO; L. DI CROCE
Lugar:
Los Cocos, Cordoba
Reunión:
Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM); 2010
Resumen:
@font-face {
font-family: "Times New Roman";
}p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: Times; }div.Section1 { page: Section1; }
Human UTX, a member of the Jumonji C
family of proteins, associates with mixed-lineage leukemia (MLL) 2/3
complexes, and during retinoic acid signaling events, the
recruitment of the UTX complex to HOX genes results in H3K27
demethylation and a concomitant methylation of H3K4. Here
we show that UTX interacts with the retinoic acid receptor (RAR) and is
involved in the differentiation of leukemic U937 cells in response to RA. UTX
occupies the promoters of key genes linked to differentiation and
regulates their transcriptional output by modulating the recruitment
of MLL 2/3 and ASC2 complexes. Moreover, overexpression of UTX in
promyelocytic NB4 cells results in enhanced cellular differentiation upon RA
treatment. Our results suggest a concerted mechanism for
transcriptional activation during differentiation in which cycles of
H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27
through UTX at RA-responsive genes.