Epigenetische Veränderungen in der Entstehung von Leukämie
Zusammenfassung der Projektergebnisse
Taken together our genome-wide identification of more than 700 high-confidence mH2A target genes suggests an important role for this histone variant in the regulation of key regulatory genes of development and cellular differentiation. Indeed, this was shown to be true in vivo by the elimination of mH2A in zebrafish embryos, which lead to severe development phenotypes. Almost one tenth of all mH2A targets encode homeobox transcription factors, which are involved in the regulation of virtually all developmental processes. Our data establishes that mH2A constitutes one of the regulatory layers that are required to ensure the correct tempo-spatial activation of these key developmental genes. Miss-regulation of homeobox genes has been implicated in various types of cancer. Future work will address the question whether and to what extent aberrant distribution of mH2A in the genome contributes to neoplasia.
Projektbezogene Publikationen (Auswahl)
- (2007) PML4 induces differentiation by Myc destabilization. Oncogene, 26, 3415-3422
Buschbeck M., Uribesalgo I., Ledl A., Gutierrez A., Müller S. and L. Di Croce
- (2008) K131dup is a recurrent cEBPa mutation in de novo acute myeloid leukemia. Ann. Hematol., 87, 819-827
Carnicer M.J., Lasa A., Buschbeck M., Serrano E., Carricondo M., Brunet S., Aventin A., Sierra J., Di Croce L., and Nomdedeu J.F.
- (2008) NURD complex facilitates chromatin alteration and changes in leukemia. Molecular Cellular Biology, epub
Morey L., Brenner C., Fazi F., Villa R., Gutierrez A., Buschbeck M., Nervi C., Minucci S., Fuks F., and L. Di Croce
