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Binding pattern and chromatin modifications induced by AML1/ETO in human hematopoietic stem/progenitor cells

ABSTRACT: The AML1/ETO fusion protein, which is present in 10% to 15% of cases of acute myeloid leukemia, is known to repress myeloid differentiation genes through DNA binding and recruitment of chromatin-modifying proteins and transcription factors in target genes. ChIP-chip analysis of human hematopoietic stem/progenitor cells transduced with the AML1/ETO fusion gene enabled us to identify 1168 AML1/ETO target genes, 103 of which were co-occupied by HDAC1 and had lost the hyperacetylation at histone H4 marks and 264 of which showed a K9 trimethylation at histone H3. Enrichment of genes involved in hematopoietic differentiation and in specific signaling pathways was observed in the presence of these epigenetic modifications associated with an inactive chromatin status. Furthermore, AML1/ETO target genes had a significant correlation between the chromatin marks studied and transcriptional silencing. ChIP-chip comparison of human hematopoietic stem/progenitor cells (HSPCs) retrovirally transduced with the AML1/ETO fusion protein with HSPCs transduced with an empty vector (Mulloy et al., Blood, 2002) using antibodies tagging the AML1/ETO fusion protein, the HDAC1 protein, as well as H4Ac and H3K9m3 chromatin modifications.

ORGANISM(S): Homo sapiens

SUBMITTER: Sara Alvarez

PROVIDER: E-GEOD-27663 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Binding pattern and chromatin modifications induced by AML1/ETO in human hematopoietic stem/progenitor cells

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