Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Chromatin accessibility, p300 and histone acetylation define PML-RARalpha- and AML1-ETO-binding sites


ABSTRACT: Chromatin accessibility is a key determinant of cell-type-specific gene expression. Here, we have investigated the chromatin architecture of different acute myeloid leukemia (AML) cells and the changes in accessibility when NB4 (APL) cells undergo the process of differentiation. For nuclease-accessible site sequencing (NA-seq; Gargiulo et al. 2009), chromatin-accessible libraries were generated in different AML leukemic cells by using restriction enzymes NlaIII and HpaII. In the case of NB4 cells, accessibility was mapped both before and after treatment with all-trans retinoic acid (ATRA) for 48hr. Differences were observed between the two conditions, and chromatin accessibility was correlated with underlying epigenetic modifications. For validation purposes, NA-seq libraries (using the NlaIII enzyme) were generated in APL and AML M1 patient's blasts. All of the ChIP-seq (Martens et al. 2010) studies were performed in leukemic NB4 and SKNO-1 cells. Supplementary file 'GSE30254_All_accessibleregions_ATRA_NB4_fseq.wig' includes data for Samples GSM749512, GSM749513, GSM749516, and GSM749517. Supplementary file 'GSE30254_All_accessibleregions_untreated_NB4_fseq.wig' includes data for Samples GSM749510, GSM749511, GSM749514, and GSM749515.

ORGANISM(S): Homo sapiens

SUBMITTER: H.G. Stunnenberg 

PROVIDER: E-GEOD-30254 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chromatin accessibility, p300, and histone acetylation define PML-RARα and AML1-ETO binding sites in acute myeloid leukemia.

Saeed Sadia S   Logie Colin C   Francoijs Kees-Jan KJ   Frigè Gianmaria G   Romanenghi Mauro M   Nielsen Fiona G FG   Raats Lianne L   Shahhoseini Maryam M   Huynen Martijn M   Altucci Lucia L   Minucci Saverio S   Martens Joost H A JH   Stunnenberg Hendrik G HG  

Blood 20120824 15


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 RARα-fusion proteins, such as PML-RARα. We used nuclease accessibility sequencing in cell lines as well as patient blasts to identify accessible DNA elements an  ...[more]

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