Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-34961E-GEOD-34959
PROVIDER: PRJNA150949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR398257.fastq.gz | Fastqsanger.gz | |||
| SRR398258.fastq.gz | Fastqsanger.gz | |||
| SRR398259.fastq.gz | Fastqsanger.gz | |||
| SRR398260.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:MIR139 is a critical tumor suppressor and commonly silenced in human cancer, including acute myeloid leukemia (AML). Here, we found that depletion of identified MIR139 targets affects AML outgrowth. We unraveled the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. Epigenetic analyses revealed two well-conserved putative enhancer regions in close proximity of transcriptional start sites (TSS) of MIR139. These regions were silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these regions abolished MIR139 transcriptional regulation in normal and oncogenic conditions. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139-silencing factor. Furthermore, direct POLR2M binding to the MIR139 TSS induced paused transcription, which was abrogated upon PRC2 inhibition. We present evidence for an oncogenic POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. Together, our findings highlight the importance of POLR2M-mediated paused transcription in AML.
2021-11-11 | PXD022488 | Pride
Project description:The transcriptional activating and repressive functions performed by Trithorax and Polycomb group complexes, respectively, are critical for to maintain cellular fates in ontogeny and in cancer. Here we report that leukemias initiated by a Trithorax-related oncogene, MLL-AF9, depend upon the Polycomb Repressive Complex 2 (PRC2) to sustain a transformed cellular state. RNAi mediated suppression of PRC2 subunits is sufficient to inhibit proliferation of MLL-AF9 leukemias, with little impact on growth of non-transformed cells. This requirement is partly due to PRC2-mediated transcriptional repression of several anti-self-renewal regulators, including Cdkn2a. These results suggest that, unlike the classical antagonism generally observed between Polycomb and Trithorax group proteins during development, the activities of these two pathways can cooperate to promote myeloid neoplasia. In order to understand downstream targets of PRC2 complex in MLL-AF9 leukemia, we performed array in murine MLL-AF9/NrasG12D cell line under the condition that two subunits of PRC2(Eed and Suz12) were suppressed by using shRNAs.
2013-07-01 | E-GEOD-34183 | biostudies-arrayexpress
Project description:Methylation of histone 3 on lysine 79 (H3K79) is broadly associated with active gene expression in eukaryotes, and the H3K79 methyltransferase DOT1L is indispensable for specific leukemia subtypes like those with MLL-translocations. We found that suppression of the histone deacetylase SIRT1 rescued MLL-AF9 leukemia cells from their dependence on DOT1L. We show that upon DOT1L inhibition, SIRT1 is required for the acquisition of a repressive chromatin state consistent with facultative heterochromatin around MLL-AF9 target genes in leukemia and other genes possess an H3K79me2(hi), H3K9ac(hi), H3K9me2(low) histone modification profile in normal hematopoietic stem and progenitor cells. Examination of histone modifications via ChIP-seq in three human cancer cell lines.
2015-03-30 | E-GEOD-62100 | biostudies-arrayexpress
Project description:Methylation of histone 3 on lysine 79 (H3K79) is broadly associated with active gene expression in eukaryotes, and the H3K79 methyltransferase DOT1L is indispensable for specific leukemia subtypes like those with MLL-translocations. We found that suppression of the histone deacetylase SIRT1 rescued MLL-AF9 leukemia cells from their dependence on DOT1L. We show that upon DOT1L inhibition, SIRT1 is required for the acquisition of a repressive chromatin state consistent with facultative heterochromatin around MLL-AF9 target genes in leukemia and other genes possess an H3K79me2(hi), H3K9ac(hi), H3K9me2(low) histone modification profile in normal hematopoietic stem and progenitor cells. Examination of histone modifications and a chromatin modifier with and without drug treatment and RNA interference.
2015-03-30 | E-GEOD-61016 | biostudies-arrayexpress
Project description:Methylation of histone 3 on lysine 79 (H3K79) is broadly associated with active gene expression in eukaryotes, and the H3K79 methyltransferase DOT1L is indispensable for specific leukemia subtypes like those with MLL-translocations. We found that suppression of the histone deacetylase SIRT1 rescued MLL-AF9 leukemia cells from their dependence on DOT1L. We show that upon DOT1L inhibition, SIRT1 is required for the acquisition of a repressive chromatin state consistent with facultative heterochromatin around MLL-AF9 target genes in leukemia and other genes possess an H3K79me2(hi), H3K9ac(hi), H3K9me2(low) histone modification profile in normal hematopoietic stem and progenitor cells. Examination of histone modifications and a chromatin modifier with and without drug treatment and RNA interference.
2015-03-30 | E-GEOD-61021 | biostudies-arrayexpress
Project description:We evaluated gene expression changes in secondary recipient murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of a homozygous conditional allele for Ezh2, a component of the Polycomb Repressive Complex2.
2012-02-22 | GSE34961 | GEO
Project description:We evaluated gene expression changes in secondary recipient murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of a homozygous conditional allele for Ezh2, a component of the Polycomb Repressive Complex2. For WT cells, 4 biological replicates were hybridized. For Ezh2-null cells, 5 biological replicates were hybridized.
2012-02-22 | E-GEOD-34961 | biostudies-arrayexpress
Project description:We evaluated gene expression changes in murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of homozygous conditional alleles for Ezh2 or Eed, both of which are components of the Polycomb Repressive Complex2.
2012-02-22 | GSE34959 | GEO
Project description:MIR139 is a tumor suppressor and commonly silenced in Acute myeloid leukemia (AML). Reactivating the expression of MIR139 eliminates AML cells. Here, we investigated the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. We found that MLL-AF9-mediated repression of MIR139 is a selective event in leukemogenesis. Analyses of Histone marks revealed two well-conserved enhancer regions, which are epigenetically silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these enhancer regions abolished transcriptional regulation of MIR139. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139 silencing factor. Furthermore, POLR2M-binding to the MIR139 transcriptional start site induces paused transcription, which is abrogated upon PRC2 inhibition. Together, we present evidence for a POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. The findings in this study highlight the importance of the transcriptional deregulation in malignant transformation.
2021-11-01 | GSE160405 | GEO
Project description:MIR139 is a tumor suppressor and commonly silenced in Acute myeloid leukemia (AML). Reactivating the expression of MIR139 eliminates AML cells. Here, we investigated the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. We found that MLL-AF9-mediated repression of MIR139 is a selective event in leukemogenesis. Analyses of Histone marks revealed two well-conserved enhancer regions, which are epigenetically silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these enhancer regions abolished transcriptional regulation of MIR139. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139 silencing factor. Furthermore, POLR2M-binding to the MIR139 transcriptional start site induces paused transcription, which is abrogated upon PRC2 inhibition. Together, we present evidence for a POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. The findings in this study highlight the importance of the transcriptional deregulation in malignant transformation.
2021-11-01 | GSE160404 | GEO