Chromatin accessibility, p300, and histone acetylation define PML-RAR? and AML1-ETO binding sites in acute myeloid leukemia. (Articolo in rivista)

Type
Label
  • Chromatin accessibility, p300, and histone acetylation define PML-RAR? and AML1-ETO binding sites in acute myeloid leukemia. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1182/blood-2011-10-386086 (literal)
Alternative label
  • Saeed S, Logie C, Francoijs KJ, Frigè G, Romanenghi M, Nielsen FG, Raats L, Shahhoseini M, Huynen M, Altucci L, Minucci S, Martens JH, Stunnenberg HG. (2012)
    Chromatin accessibility, p300, and histone acetylation define PML-RAR? and AML1-ETO binding sites in acute myeloid leukemia.
    in Blood
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Saeed S, Logie C, Francoijs KJ, Frigè G, Romanenghi M, Nielsen FG, Raats L, Shahhoseini M, Huynen M, Altucci L, Minucci S, Martens JH, Stunnenberg HG. (literal)
Pagina inizio
  • 3058 (literal)
Pagina fine
  • 3068 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 120(15) (literal)
Rivista
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Radboud University, Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; Centre for Molecular and Biomolecular Informatics, Radboud University, Nijmegen, The Netherlands; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, The Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Dipartimento di Patologia Generale, Seconda Universita degli Studi di Napoli, Napoli, Italy; IGB-CNR, Napoli, Italy; and Department of Biomolecular Sciences and Biotechnology, University of Milan, Milan, Italy (literal)
Titolo
  • Chromatin accessibility, p300, and histone acetylation define PML-RAR? and AML1-ETO binding sites in acute myeloid leukemia. (literal)
Abstract
  • Chromatin accessibility plays a key role in regulating cell type specific gene expression during hematopoiesis but has also been suggested to be aberrantly regulated during leukemogenesis. To understand the leukemogenic chromatin signature, we analyzed acute promyelocytic leukemia, a subtype of leukemia characterized by the expression of RAR?-fusion proteins, such as PML-RAR?. We used nuclease accessibility sequencing in cell lines as well as patient blasts to identify accessible DNA elements and identified > 100 000 accessible regions in each case. Using ChIP-seq, we identified H2A.Z as a histone modification generally associated with these accessible regions, whereas unsupervised clustering analysis of other chromatin features, including DNA methylation, H2A.Zac, H3ac, H3K9me3, H3K27me3, and the regulatory factor p300, distinguished 6 distinct clusters of accessible sites, each with a characteristic functional makeup. Of these, PML-RAR? binding was found specifically at accessible chromatin regions characterized by p300 binding and hypoacetylated histones. Identifying regions with a similar epigenetic make up in t(8;21) acute myeloid leukemia (AML) cells, another subtype of AMLs, revealed that these regions are occupied by the oncofusion protein AML1-ETO. Together, our results suggest that oncofusion proteins localize to accessible regions and that chromatin accessibility together with p300 binding and histone acetylation characterize AML1-ETO and PML-RAR? binding sites (literal)
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