A reciprocal translocation involving chromosomes 8 and 21 generates the AML1/ETO oncogenic transcription factor that initiates acute myeloid leukemia by recruiting co-repressor complexes to DNA. AML1/ETO interferes with the function of its wild-type counterpart, AML1, by directly targeting AML1 binding sites. However, transcriptional regulation determined by AML1/ETO probably relies on a more complex network, since the fusion protein has been shown to interact with a number of other transcription factors, in particular E-proteins, and may therefore target other sites on DNA. Genome-wide chromatin immunoprecipitation and expression profiling were exploited to identify AML1/ETO-dependent transcriptional regulation. AML1/ETO was found to co-localize with AML1, demonstrating that the fusion protein follows the binding pattern of the wild-type protein but does not function primarily by displacing it. The DNA binding profile of the E-protein HEB was grossly rearranged upon expression of AML1/ETO, and the fusion protein was found to co-localize with both AML1 and HEB on many of its regulated targets. Furthermore, the level of HEB protein was increased in both primary cells and cell lines expressing AML1/ETO. Our results suggest a major role for the functional interaction of AML1/ETO with AML1 and HEB in transcriptional regulation determined by the fusion protein.
AML1/ETO oncoprotein is directed to AML1 binding regions and co-Localizes with AML1 and HEB on its targets / A. Gardini, M. Cesaroni, L. Luzi, A.J. Okumura, J.R. Biggs, S.P. Minardi, E. Venturini, D.E Zhang, P.G. Pelicci, M. Alcalay. - In: PLOS GENETICS. - ISSN 1553-7390. - 4:11(2008 Nov), p. e1000275.e1000275.
|Titolo:||AML1/ETO oncoprotein is directed to AML1 binding regions and co-Localizes with AML1 and HEB on its targets|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||nov-2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pgen.1000275|
|Appare nelle tipologie:||01 - Articolo su periodico|