2026-05-21T23:54:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/261802025-12-18T12:56:59Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Maiques-Diaz, A
author
Chou, F S
author
Wunderlich, M
author
Gómez-López, G
author
Jacinto, F V
author
Rodriguez Perales, Sandra
author
Larrayoz, M J
author
Calasanz, M J
author
Mulloy, J C
author
Cigudosa, J C
author
Alvarez, S
funder
ASOCIACION ESPAÑOLA CONTRA EL CANCER
funder
United States Department of Health & Human Services National Institutes of Health (NIH) - USA
funder
MINISTERIO DE CIENCIA Y COMPETITIVIDAD (ESPAÑA)
2025-01-28T16:55:33Z
2025-01-28T16:55:33Z
2012-06
Leukemia . 2012 Jun;26(6):1329-37
Leukemia
22289984
https://hdl.handle.net/20.500.12105/26180
The AML1-ETO fusion protein, which is present in 10-15% 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 histone deacetylase 1 (HDAC1) and had lost the hyperacetylation mark at histone H4, and 264 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. Interestingly, AML1 binding sites were absent on a large number of selected AML1-ETO promoters and an Sp1 binding site was found in over 50% of them. Reversible silencing induced by the fusion protein in the presence of AML1 and/or Sp1 transcription factor binding site was confirmed. Therefore, this study provides a global analysis of AML1-ETO functional chromatin modifications and identifies the important role of Sp1 in the DNA binding pattern of AML1-ETO, suggesting a role for Sp1-targeted therapy in this leukemia subtype.
eng
AML1-ETO
myeloid leukemia
histone deacetylation
H3K9me3
SP1
Chromatin modifications induced by the AML1-ETO fusion protein reversibly silence its genomic targets through AML1 and Sp1 binding motifs.
research article
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