Ontology highlight
ABSTRACT:
PROVIDER: PRJNA243849 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1220080.fastq.gz | Fastqsanger.gz | |||
| SRR1220081.fastq.gz | Fastqsanger.gz | |||
| SRR1220082.fastq.gz | Fastqsanger.gz | |||
| SRR1220083.fastq.gz | Fastqsanger.gz | |||
| SRR1220084.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 7 |
Similar Datasets
Project description:Impact of human MLL/COMPASS and Polycomb complexes on the DNA methylome [expression array]
| PRJNA243852 | ENA
Project description:Impact of human MLL/COMPASS and Polycomb complexes on the DNA methylome [MBD-seq]
| PRJNA243850 | ENA
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:COMPASS and Polycomb complexes are antagonistic chromatin complexes that are frequently inactivated in cancers, but how their inactivation affects the cellular hierarchy, composition and growth of tumors is unclear. Such characteristics can be systematically investigated in Drosophila neuroblast tumors in which cooption of temporal patterning induces a developmental hierarchy that confers cancer stem cell (CSC) properties to a subset of neuroblasts retaining an early larval temporal identity. Here, using single-cell transcriptomics, we reveal that the trithorax/MLL1/2-COMPASS-like complex guides the developmental trajectory at the top of the tumor hierarchy. Consequently, trithorax inactivation drives larval-to-embryonic temporal reversion and the dramatic expansion of CSCs that remain locked in a spectrum of early temporal states. Surprisingly, this phenotype is amplified by concomitant inactivation of Polycomb Repressive Complex 2 genes, unleashing tumor growth. This study exemplifies how inactivation of specific COMPASS and Polycomb complexes cooperates to impair tumor hierarchies and induce CSC plasticity and heterogeneity.
2021-08-31 | GSE179154 | GEO
Project description:Methylation of lysine 4 at histone H3 (H3K4) at promoters is tightly linked to transcriptional regulation in human cells. At least six different COMPASS-like multi-subunit (SET1/MLL) complexes have been described that contain methyltransferase activity towards H3K4, but a comprehensive and quantitative analysis of these SET1/MLL complexes is lacking. We applied label-free quantitative mass spectrometry to determine the subunit composition and stoichiometry of the human SET1/MLL complexes. Peptides were applied to online nanoLC-MS/MS, using a 120 min acetonitrile gradient (5.6 - 76%). Mass spectra were recorded on an LTQ-Orbitrap-Velos mass spectrometer (Thermo) selecting the 15 most intense precursor ions of every full scan for fragmentation. Raw data were analyzed using MaxQuant 1.3.0.5, with label-free quantification (LFQ), match between runs (between triplicates) and the iBAQ algorithm enabled. MaxQuant default settings were used for peptide identification; Enzyme: Trypsin/P, MS tolerance (FTMS): 6 ppm, max missed cleavages: 2, max charge: 7, MS/MS tolerance (ITMS): 0.5 Da, Peptide FDR: 0.01 and Protein FDR: 0.01. Normalized mass spectrometric intensities (LFQ intensities) were compared between the GFP-tagged and control sample, using an adapted permutation-based false discovery rate (FDR) t-test in Perseus (MaxQuant package).
2013-09-13 | PXD000172 | 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.
2013-07-01 | GSE34183 | GEO
Project description:The evolutionally conserved COMPASS complexes are responsible for the catalyzation of H3K4 methylations. Recently, three types of COMPASS complexes which contains histone methyltransferases ATX1/2, ATX3, or ATX4/5 were identified in Arabidopsis. Here, we report the ATX proteins are essential for the survival of Arabidopsis. By RNA-seq and chromatin immunoprecipitation (ChIP-seq) analysis, we found ATX1/2-, ATX3-, and ATX4/5-containing COMPASS complex redundantly regulate gene expression and H3K4me3 modifications. In addition to the developmental-related genes, we found the expression of DNA methylation-related genes were also regulated by the COMPASS complexes. The transcript and H3K4me3 levels at the RdDM pathway genes (NRPE1, DCL3, IDN2, FDM2) and at the DNA demethylase encoding genes (ROS1, DML2, DML3) were down-regulated in atx1/2/4/5 mutants. Via bisulfate sequencing, we found the atx1/2/4/5 showed hypermethylation at CG and CHG contexts whereas the hypomethylation at CHH contexts. By comparing the differentially methylated regions (DMRs) in atx1/2/4/5 with that in ros1;dml2;dml3 (rdd) and in nrpe1, a large part of overlapping DMRs were identified. Based on these results and other findings, we propose that the hypermethylation in CG and CHG is partially caused by the down-regulation of ROS1/DML2/DML3, and the hypomethylation in CHH is mainly caused by the down-regulation of NRPE1. Furthermore, we revealed that the COMPASS complexes also play a redundant role in regulating the transcription of transposable elements (TEs). This study extends our knowledge about the function of COMPASS in plant development and illustrate the important roles for COMPASS complexes in the regulation of DNA methylation and TEs transcription.
2022-11-14 | GSE206685 | GEO
Project description:Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. The Set1/COMPASS was the founding member and the only H3K4 methylases in S. cerevisiae, however, in mammals at least six H3K4 methylases Set1A/B and MLL1-4 are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wide analysis of H3K4 methylation pattern in wild-type Mll1+/+ and Mll1-/- mouse fibroblasts (MEFs). We found that Mll1 is required for the H3K4 trimethylation of less than 5% of promoters carrying this modification. Many of these genes, which include developmental regulators such as Hox genes show decreased levels of RNA polymerase II recruitment and expression concomitant with the loss of H3K4 methylation. Although Mll1 is only required for the methylation of a subset of Hox genes, Menin, a component of the Mll1 and Mll2 complexes, is required for the overwhelming majority of H3K4 methylation at Hox loci. However, the loss of MLL3/4 and/or the Set1 complexes have little to no effect on the Hox loci H3K4 methylation or expression levels in these MEFs. Together these data provide insight into redundancy and specialization of COMPASS-like complexes in mammals and provide evidence on a possible role for Mll1-mediated H3K4 methylation in the regulation of transcriptional initiation. Expression arrays were done with Mll1+/+ and Mll1-/- mouse embryonic fibroblasts. Four replicates were done (dyes were swapped). DNA was hybridized to Agilent Mouse Whole Genome Expression Arrays (4x44k).
2009-10-20 | E-GEOD-18261 | biostudies-arrayexpress
Project description:An epigenetic mark of polycomb response elements implemented by Trx/MLL/COMPASS
| PRJNA322547 | ENA
Project description:Precise dynamic control of activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent gene promoters is essential for normal development and frequently corrupted in cancer. Using whole genome CRISPR/Cas9 screens we identify specific roles for MTF2-PRC2.1 and PCGF1-PRC1.1 polycomb complexes, and MLL1/2-COMPASS-like complex components in maintaining bivalency. Contrary to expectations, loss of Menin or inhibition of the Menin-MLL1/2 interaction, induces activation of bivalent genes via loss of polycomb-mediated repression and defines distinct roles for MLL1/2 and Menin in gene regulation. Whilst Menin and MLL1/2 contribute to maintenance H3K4me3 at active genes, a separate Menin-independent function of MLL1/2 opposes polycomb mediated repression at bivalent genes. MLL1/2 are essential for basal transcription and, although dispensable for transcription factor driven activation, facilitate transcriptional consistency during dynamic changes in gene expression. This functional partitioning of COMPASS complex components reveals therapeutic opportunities to target oncogenic and immunosuppressive functions of PRC2 through pharmacological inhibition of Menin.
2023-01-13 | GSE181823 | GEO