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|Titolo:||Redistribution of H3K27me3 and acetylated histone H4 upon exposure to azacitidine and decitabine results in de-repression of the AML1/ETO target gene IL3.|
|Autori interni:||BUCHI, FRANCESCA|
VALENCIA MARTINEZ, ANA BELEN
|Data di pubblicazione:||2014|
|Abstract:||Human acute myeloid leukemia is characterized by a block in maturation caused by genetic and epigenetic alterations. We studied the effects of low concentrations of the DNA methyltransferase (DNMT) inhibitors 5-azacitidine and decitabine on apoptosis and on chromatin remodeling in an AML1/ETO inducible model of human AML. While both DNMT inhibitors induced apoptosis, only azacitidine did so via caspase activation, possibly through its exclusive non-DNA depending effects. We evaluated histone marks for permissive chromatin, H3K4me3 and acetylated histone H4, and for nonpermissive chromatin, H3K9me2 and H3K27me3, at the promoter of the IL3 gene, which is under the direct control of AML1/ETO and is critical for myeloid maturation. We observed that low concentrations of DNMT inhibitors induced a loss of H3K27me3 and gain of acetylated histone H4 at the IL3 promoter exclusively in AML1/ETO-positive cells, which was associated with transcriptional reactivation of the IL3 gene.|
|Appare nelle tipologie:||1a - Articolo su rivista|
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