Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA179153 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE42044: DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (sequencing) GSE42118: DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (Illumina Methylation) Refer to individual Series
2012-11-08 | E-GEOD-42119 | biostudies-arrayexpress
Project description:DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding
| PRJNA179155 | ENA
Project description:DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (sequencing)
| PRJNA179154 | ENA
Project description:A global view of PML-RAR? transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. Complete Abstract: The translocation t(15;17) generates the chimeric PML-RAR? transcription factor that is the initiating event of acute promyelocytic leukemia. A global view of PML-RAR? transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. ChIP-chip experiments identified 372 direct genomic PML-RAR? targets. A subset of these was confirmed in primary acute promyelocytic leukemia. Direct PML-RARá targets include regulators of global transcriptional programs as well as critical regulatory genes for basic cellular functions such as cell cycle control and apoptosis. PML-RAR? binding universally led to HDAC1 recruitment, loss of histone H3 acetylation, increased tri-methylation of histone H3 lysine 9 and unexpectedly increased tri-methylation of histone H3 lysine 4. The binding of PMLRAR? to target promoters and the resulting histone modifications resulted in mRNA repression of functionally relevant genes. Taken together our results reveal that the transcription factor PML-RAR? regulates key cancer related genes and pathways by inducing a repressed chromatin formation on its direct genomic target genes. Keywords: ChIP on Chip U937 transfected with an inducible PML-RAR?/empty vecor were induced, harvested and Chromatin-Ips for PML, AcH3 followed by microarray hybridasation were carried out. For detailed procedures see Hoemme et al. "Chromatin modifications induced by PML-RARalpha repress critical targets in leukemogenesis as analyzed by ChIP-Chip"
2008-09-06 | E-GEOD-12641 | biostudies-arrayexpress
Project description:A global view of PML-RARα transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. Complete Abstract: The translocation t(15;17) generates the chimeric PML-RARα transcription factor that is the initiating event of acute promyelocytic leukemia. A global view of PML-RARα transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. ChIP-chip experiments identified 372 direct genomic PML-RARα targets. A subset of these was confirmed in primary acute promyelocytic leukemia. Direct PML-RARá targets include regulators of global transcriptional programs as well as critical regulatory genes for basic cellular functions such as cell cycle control and apoptosis. PML-RARα binding universally led to HDAC1 recruitment, loss of histone H3 acetylation, increased tri-methylation of histone H3 lysine 9 and unexpectedly increased tri-methylation of histone H3 lysine 4. The binding of PMLRARα to target promoters and the resulting histone modifications resulted in mRNA repression of functionally relevant genes. Taken together our results reveal that the transcription factor PML-RARα regulates key cancer related genes and pathways by inducing a repressed chromatin formation on its direct genomic target genes. Keywords: ChIP on Chip
2008-09-06 | GSE12641 | GEO
Project description:The origin of aberrant DNA methylation in cancer remains largely unknown. In this study, we elucidated the DNA methylome in primary Acute Promyelocytic Leukemia (APL) and the role of PML-RARa in establishing these patterns. APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes and remission bone marrow. A core set of differentially methylated regions in APL was identified. Age at diagnosis, Sanz score and Flt3-mutation status characterized methylation subtypes. Transcription factor binding sites, e.g. c-myc binding sites were associated with low methylation. SUZ12 and REST binding sites identified in embryonic stem cells were, however, preferentially DNA hypermethylated in APL. Unexpectedly, PML-RARa binding sites were also protected from aberrant DNA methylation in APL. In line, myeloid cells from pre-leukemic PML-RARa knock-in mice did not show altered DNA methylation and expression of PML-RARa in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. ATRA treatment of APL blasts did also not result in DNA methylation changes. These results suggest that aberrant DNA methylation is associated with leukemia phenotype but not required for PML-RARa-mediated initiation of leukemogenesis. Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2012-11-08 | E-GEOD-42118 | biostudies-arrayexpress
Project description:Acute promyelocytic leukemia (APL) is associated with PML-RARA expression and late myeloid maturation arrest. The myeloid restriction of PML-RARA dependent leukemia has been recapitulated in multiple mouse models of APL, including PML-RARA expressed from the Ctsg locus (mCG-PR). However, we report here that Ctsg expression is not limited to promyelocytes (as had previously been thought); Ctsg RNA is detectable in KLS cells, and mCG-PR mice express PML-RARA within the same compartment, an event that alters multilineage hematopoiesis. However, these animals only develop myeloid leukemia (consistent with the myeloid restriction of human PML-RARA-associated leukemia). Our results suggest that APL is shaped by myeloid- and development-specific factors that define the ultimate leukemic phenotype rather than PML-RARA acting in a committed myeloid precursor.
2010-10-21 | GSE24728 | GEO
Project description:A novel NUP98/RARG gene fusion in acute myeloid leukemia resembling acute promyelocytic leukemia
2010-10-18 | E-MEXP-2928 | biostudies-arrayexpress
Project description:Acute Promyelocytic Leukemia is characterized by the accumulation in the blood and bone marrow of promyelocytes. The PML/RARα fusion protein is identified as the primary abnormality implicated in the pathology, and is believed to prevent transcription of genes necessary for normal myeloid development and differentiation. Identifying its targets is critical to comprehend the road to pathogenesis. To understand how PML/RARα, in the absence of secondary lesions, alters gene expression, DNA methylation and proliferation we used a novel experimental and sorting strategy to study normal versus preleukemic promyelocytes in vivo. Expression and methylation profiling analyses were performed on highly purified samples. Surprisingly, despite its ability to initiate leukemia, PML/RARα had overall minor effects on both the transcriptome and epigenome. Important regulators of the myeloid maturation program were not altered but, remarkably, PML/RARα promyelocytes showed strong downregulation of secondary and tertiary granule genes. Subtle changes were also observed on the DNA methylation profile, with PML/RARα predominantly mediating hypomethylation. We performed intersection studies between altered loci and previously described PML/RARα binding sites but found little overlap. Importantly, we show for the first time that PML/RARα on its own increases proliferation, and that this increased proliferation correlates with the ability to initiate leukemia. DNA methylation profiling in CD34(+) early promyelocytes and CD34(-) late promyelocytes cells from PML-RARa transgenic mice vs. control mice.
2015-09-04 | E-GEOD-54038 | biostudies-arrayexpress
Project description:Acute promyelocytic leukemia (APL) is associated with PML-RARA expression and late myeloid maturation arrest. The myeloid restriction of PML-RARA dependent leukemia has been recapitulated in multiple mouse models of APL, including PML-RARA expressed from the Ctsg locus (mCG-PR). However, we report here that Ctsg expression is not limited to promyelocytes (as had previously been thought); Ctsg RNA is detectable in KLS cells, and mCG-PR mice express PML-RARA within the same compartment, an event that alters multilineage hematopoiesis. However, these animals only develop myeloid leukemia (consistent with the myeloid restriction of human PML-RARA-associated leukemia). Our results suggest that APL is shaped by myeloid- and development-specific factors that define the ultimate leukemic phenotype rather than PML-RARA acting in a committed myeloid precursor. Bone marrow from individual mice expressing PML-RARA from the murine Ctg locus (mCG-PR) and littermate controls was harvested from both femurs and tibia. Standard cell lysis was performed and total RNA was extracted from the flow sorted KLS and SLAM cells. A total of 13 specimens including 3 x mCG-PR_KLS_6wks, 2 x mCG-PR_KLS_13wks,2 x mCG-PR_SLAM_7wks, 4 x WT_KLS_12-13wks (control) and 2 x WT_SLAM_6wks (control) were analyzed using Affymetrics Mouse Exon 1.0 ST platform.
2010-10-21 | E-GEOD-24728 | biostudies-arrayexpress