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Series GSE18886 Query DataSets for GSE18886
Status Public on Dec 17, 2009
Title PML-RARa/RXR alters the epigenetic landscape in Acute Promyelocytic Leukemia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Many different molecular mechanisms have been suggested to be associated with PML-RAR dependent transformation of haematopoietic progenitors. Here, we investigated the role of PML-RAR and RXR in the organization of epigenetic structures at a genome-wide level. We identified 2722 high confidence PML-RAR binding sites in the leukemic model cell line NB4 and found PML-RAR colocalization with RXR to the vast majority of these binding regions. Importantly, these results could be corroborated and extended in primary blast cells of two APL patients. Through genome-wide epigenetic studies we show that treatment with pharmacological doses of all-trans retinoic acid ATRA induces global alterations in active H3 acetylation and repressive H3K27me3, H3K9me3 and DNA methylation chromatin modifications. However at the PML-RAR/RXR binding sites, ATRA only induces changes in H3 acetylation. These H3 acetylation alterations triggered by the loss of PML-RAR/RXR binding affect H3 acetylation and RNA polymerase II occupancy at nearby genes. Our results suggest that PML-RAR/RXR functions as a local chromatin modulator and that specific recruitment of histone deacetylase activities to genes important for haematopoietic differentiation, RAR signaling and epigenetic control is crucial to the transforming potential of PML-RAR/RXR.
 
Overall design Examination of PML, RARa and RXR binding sites in leukemic cells before and after ATRA treatment, association with transcription via RNAPII occupancy and with chromatin modifications.
 
Contributor(s) Stunnenberg HG, Martens JH, Brinkman AB, Simmer F, Francoijs K, Nebbioso A, Ferrara F, Altucci L
Citation(s) 20159609
Submission date Nov 04, 2009
Last update date May 15, 2019
Contact name H.G. Stunnenberg
E-mail(s) h.stunnenberg@ncmls.ru.nl
Phone +31-24-3610520
Organization name Radboud University
Department Department of Molecular Biology (274)
Street address Geert Grooteplein 28
City Nijmegen
ZIP/Postal code 6525 GA
Country USA
 
Platforms (1)
GPL9052 Illumina Genome Analyzer (Homo sapiens)
Samples (40)
GSM468180 PML_ChIP-seq_NB4_noATRA, JM1a and JM1b
GSM468181 RXR_ChIP-seq_NB4_noATRA, JM2a and JM2b
GSM468182 RAR_ChIP-seq_NB4_noATRA, JM3
Relations
SRA SRP001549
BioProject PRJNA121283

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE18886_RAW.tar 4.2 Gb (http)(custom) TAR (of BED, WIG)
GSE18886_ratio_of_tags.txt.gz 904.4 Kb (ftp)(http) TXT
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA
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