Mus musculus
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR224572.fastq.gz | Fastqsanger.gz | |||
| DRR224573.fastq.gz | Fastqsanger.gz | |||
| DRR224574.fastq.gz | Fastqsanger.gz | |||
| DRR224575.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Chromosome translocations involving the MLL gene are common rearrangements in leukemia. Such translocations fuse the MLL 5’-region in frame to partner genes , and the resultant fusion proteins can cause MLL-related leukemia. MLL-fusions activate transcription of target genes such as the HoxA cluster and Meis1, but the underlying mechanisms remain elusive. We found that the MLL-AF10 fusion recruits Tip60 to the Hoxa9 locus, where it acetylates H2A.Z, thereby promoting Hoxa9 expression. Following conditional deletion of Tip60, hypoacetylation of H2A.Z was accompanied by recruitment of Ezh2, the catalytic subunit of PRC2, suggesting that nucleosomes with hypoacetylated H2A.Z are the preferential targets of Ezh2. Our findings suggest that MLL-AF10 achieves active chromatin states by recruiting Tip60, which acetylates H2A.Z to prevent gene silencing by Ezh2.
2021-06-30 | GSE142557 | GEO
Project description:Expression profiling of MLL-AF10 myeloid leukemia cellular subsets
| PRJNA114579 | ENA
Project description:Nuclear receptor-binding SET domain protein 1 (NSD1) prototype is a family of mammalian histone methyltransferases (NSD1, NSD2/MMSET/WHSC1, NSD3/WHSC1L1) that are essential in development and are mutated in human acute myeloid leukemia (AML), overgrowth syndromes, multiple myeloma and lung cancers. In AML, the recurring t(5;11)(q35;p15.5) translocation fuses NSD1 to nucleoporin-98 (NUP98). Here, we present the first characterization of the transforming properties and molecular mechanisms of NUP98-NSD1. We demonstrate that NUP98-NSD1 induces AML in vivo, sustains self-renewal of myeloid stem cells in vitro, and enforces expression of the HoxA7, HoxA9, HoxA10 and Meis1 proto-oncogenes. Mechanistically, NUP98-NSD1 binds genomic elements adjacent to HoxA7 and HoxA9, maintains histone H3 Lys 36 (H3K36) methylation and histone acetylation, and prevents EZH2-mediated transcriptional repression of the Hox-A locus during differentiation. Deletion of the NUP98 FG-repeat domain, or mutations in NSD1 that inactivate the H3K36 methyltransferase activity or that prevent binding of NUP98-NSD1 to the Hox-A locus precluded both Hox-A gene activation and myeloid progenitor immortalization. We propose that NUP98-NSD1 prevents EZH2-mediated repression of Hox-A locus genes by colocalizing H3K36 methylation and histone acetylation at regulatory DNA elements. This report is the first to link deregulated H3K36 methylation to tumorigenesis and to link NSD1 to transcriptional regulation of the Hox-A locus. Experiment Overall Design: Total RNA was extracted from stably transformed progenitors cultured in vitro and the expression levels of mRNA transcripts quantified using the Affymetrix GeneChip Mouse Genome 430 2.0 array, as previously described. The GEO database accession numbers: for progenitors immortalized by HoxA9 (GSM190542, GSM190546, GSM190547); for progenitors immortalized by coexpressed HoxA9 plus Meis1 (GSM190548, GSM190549, GSM190550); for progenitors immortalized by NUP98-NSD1 (GSM190551, GSM190552, GSM190553); and for progenitors immortalized by MLL-ENL (GSM190554). Experiment Overall Design: NOTE: CEL files and dChip data were requested by GEO but not provided.
2008-06-11 | E-GEOD-10071 | biostudies-arrayexpress
Project description:Chromosome translocations involving the MLL gene are common rearrangements in leukemia. Such translocations fuse the MLL 5’-region in frame to partner genes , and the resultant fusion proteins can cause MLL-related leukemia. MLL-fusions activate transcription of target genes such as the HoxA cluster and Meis1, but the underlying mechanisms remain elusive. We found that the MLL-AF10 fusion recruits Tip60 to the Hoxa9 locus, where it acetylates H2A.Z, thereby promoting Hoxa9 expression. Following conditional deletion of Tip60, hypoacetylation of H2A.Z was accompanied by recruitment of Ezh2, the catalytic subunit of PRC2, suggesting that nucleosomes with hypoacetylated H2A.Z are the preferential targets of Ezh2. Our findings suggest that MLL-AF10 achieves active chromatin states by recruiting Tip60, which acetylates H2A.Z to prevent gene silencing by Ezh2.
2021-06-30 | GSE142558 | GEO
Project description:Cooperation of MLL/AF10 with RAS pathway mutations accelerated myeloid leukemia development. The detail molecular mechanism is analyzed by identification of the differentially expressed genes between MLL/AF10 cells harboring wild-type and mutant RAS pathway genes and by with or without Hoxa11. We used cDNA microarray to compare transcriptomes between mouse MLL/AF10 myeloid leukemia cells harboring wild-type KRAS and harboring KRAS-G12C (AKw1G and AK3G), or between MLL/AF10 cells harboring wild-type PTPN11 and harboring PTPN11-G503A (APw-1 and APm-1), or between MLL/AF10 cells without and with Hoxa11 (12G-V and 12G-H11).
2020-07-01 | GSE134586 | GEO
Project description:Background: MLL (KMT2A)-EB1 (MAPRE1) fusion was identified in a patient with de novo pro-B acute lymphoblastic leukemia. To investigate the leukemogenesis of MLL-EB1 fusion, a retroviral transduction of MLL-EB1 to murine bone marrow cells was performed. A frequent MLL fusion, MLL-AF10(OM-LZ), was used as a positive control. Results: Two MLL-EB1 immortalized cell lines (ME1 and ME2G), and a MLL-AF10(OM-LZ) immortalized cell line (12G) were generated. Microarray results showed that many genes including Evi1 and Ets1 were differentially expressed in ME1/ME2G and 12G cell lines.
2017-06-02 | GSE82156 | GEO
Project description:Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes. Primary MLL-AF9 leukemias in the AF10 floxed background (homozygous) were transduced with MSCV-IRES-tdTomato (MIT) or the Cre recombinase expressing MIT vector, cells were sorted and injected into secondary recipient mice to generate Af10 floxed (MIT) or deleted (CRE) leukemias. BM cells fresly harvested from these leukemias were sorted for tdTomato expression and used for microarrays. BM cells from Hoxa9-Meis1 transduced primary leukemias were used for comparison.
2014-09-08 | E-GEOD-54499 | biostudies-arrayexpress
Project description:The clinical and cytogenetic features associated with T-cell acute lymphoblastic leukemia (T-ALL) are not predictive of early treatment failure or relapse. We investigated 213 newly diagnosed patients who were treated in the Children's Oncology Group (COG) T-ALL Studies 9404 and 0434 and identified a cluster cases characterized by increased expression of HOX9/10. In samples with >8-fold HOXA9/10 deregulation, the presence of specific molecular lesions were confirmed through a systematic review of cytogenetic databases, FISH and PCR testing. In cases with no identifiable lesions using the methods above, RNA sequencing was performed (Illumina and Ion Proton). Fifteen cases selected for RNA sequencing met three criteria: HOXA9/10 expression ≥8-fold above the median, sufficient RNA, and an incomplete or absent molecular explanation for each sample’s HOXA9/10 deregulation. Three cases were confirmed to have PICALM-AF10 fusions. Two additional AF10-R cases showed DDX3X-AF10 lesions, one of which harbored a novel CASK gene fragment in a complex CASK-DDX3X-AF10 translocation. Two cases harbored NUP98 fusions46 and one case each was identified for MLL-AF6, MLL-PICALM, HOXA10-(3’UTR)TRBC45, STAG2-LMO2, LOC338817-CCDC91. We could not identify fusion transcripts in 3 cases.
2017-06-29 | GSE71359 | GEO
Project description:From mice, strand-specific RNA-Seq of granulocyte-myeloid progenitors (GMP) and hematopoietic stem cells (HSC). Cancer stem cells (CSC) were created with MLL-ENL transfections using puromycin for both GMP and HSCs. Further knock-outs were created of -catenin (Ctnnb1) and Hoxa9.
2017-10-10 | E-MTAB-3647 | biostudies-arrayexpress
Project description:The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Samples are from five separate cohorts of mice where leukemia was initiated using distinct MLL fusion oncogenes: MLL-AF1p (n=9), MLL-AF10 (n=8), MLL-GAS7 (n=5), MLL-AF9 (n=5) and MLL-ENL (n=7). Four normal BM samples were also used as controls.
2009-02-21 | E-GEOD-13690 | biostudies-arrayexpress