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Unknown,Transcriptomics,Genomics,Proteomics

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Leukemogenic MLL-ENL fusions induce alternative chromatin states to drive a functionally dichotomous group of target genes

ABSTRACT: MLL fusions are leukemogenic transcription factors that enhance transcriptional elongation through modification of chromatin and RNAPolII. Global transcription rates and chromatin changes accompanying the transformation process were monitored by nascent-RNA-seq and ChIP-seq identifying 165 targets separated into two distinct clades. ChIP-seq data complementing this RNA-seq data set can be found in ArrayExpress under accession number E-MTAB-3593 (http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3593)

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Robert Slany

PROVIDER: E-MTAB-3591 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Leukemogenic MLL-ENL fusions induce alternative chromatin states to drive a functionally dichotomous group of target genes

Project description:MLL fusions are leukemogenic transcription factors that enhance transcriptional elongation through modification of chromatin and RNAPolII. Global transcription rates and chromatin changes accompanying the transformation process were monitored by nascent-RNA-seq and ChIP-seq identifying 165 targets separated into two distinct clades. This accession contains ChIP Seq experiments for MLLENL and a negative control. The RNA-seq data set could also be found in ArrayExpress under accession number E-MTAB-3591 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3591/ ).

2016-03-31 | E-MTAB-3593 | biostudies-arrayexpress

ChIP-seq of CD117-positive primary hematopoietic precursor cell from Meer mice that carry a leukemogenic knock-in of an inducible ENL-ER portion into the mouse Mll locus

Project description:This ChIP-seq experiment was done to investigate the global distribution of H2A ubiquitination (a hallmark of polycomb mediated repression), H2B ubiquitination (introduced by PAF-complex associated ubiquitin ligases and connected to active transcription), and PAF1 occupation in Meer cells. Meer cells are primary cells transformed by a knock-in of an inducible Mll-ENL oncogene. ENL and ENLins ChIP-seqs were done in CD117-positive primary hematopoietic cells without any pretransformation by other oncogenes.

2018-01-23 | E-MTAB-5569 | biostudies-arrayexpress

Determination of HOXA1 and HOXA9 target genes with inducible HOX constructs

Project description:Target genes of HOXA1 and HOXA9 were determined with the help of inducible HOX-ER constructs. For this purpose bone marrow was harvested from C57BL/6 mice and c-Kit positive progenitors were enriched by magnetic sorting (MACS technology, Miltenyi, Germany). After retroviral infection by spinoculation the cells were plated for three rounds in methylcellulose. Subsequently cells were maintained in liquid culture in RPMI1640 supplemented with murine recombinant cytokines at 100ng/ml (stem cell factor) and 10ng/ml (IL-3, IL-6, granulocyte/macrophage-colony stimulating factor) as well as 100nM 4-hydroxy-tamoxifen (TAM) for HOX activation.<br><br>For microarray analysis 4 independent cell lines were created for each HOX construct. RNA was isolated from cells in the presence of TAM and 72h after withdrawal of the inductor. Pairs of RNA replicates were pooled and two +TAM as well as two -TAM duplicates per HOX gene were hybridized to Agilent44K mouse expression arrays. Array processing and evaluation was done commercially according to Agilent specifications by ImaGenes (now SourceBioScience), Berlin, Germany.

2012-11-02 | E-MEXP-3648 | biostudies-arrayexpress

Homeodomain dependent gene expression in HOX transformed primary cells

Project description:The gene expression profile was determined in primary cells transformed by two different HOX genes (HOXA1 and HOXA9) and by two HOX derivatives where the homeodomain was exchanged.

2013-01-31 | E-MEXP-3617 | biostudies-arrayexpress

Expression profiles of mouse NK cell subsets

Project description:It is known that NK cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of four murine NK cell subsets distinguished by CD117 (c-kit), CD27 and CD11b expression. Gene expression was measured in NK cell subsets freshly sorted from murine C57Bl/6 splenocytes. Two to three different batches were analysed.

2016-04-01 | E-GEOD-45842 | biostudies-arrayexpress

MLL Fusion Proteins Preferentially Regulate a Small Set of Wild Type MLL Target Genes in the Leukemic Genome

Project description:MLL encodes a histone methyltransferase that is critical in maintaining gene expression during embryonic development and hematopoiesis. 11q23 translocations encode chimeric MLL fusions that act as potent drivers of acute leukemia. However, it remains unclear what portion of the leukemic genome is under the direct control of the MLL fusion protein. By comparing patient-derived leukemic cell lines, we find that MLL fusion-bound genes are a small subset of that recognized by wild-type MLL. In an inducible MLL-ENL cellular model, binding of the MLL fusion protein and changes in H3K79 methylation are limited to a specific portion of the genome, whereas wild-type MLL distributes to a much larger set of gene loci. Surprisingly, among 223 MLL fusion-bound genes, only 12 demonstrate a significant increase in mRNA expression upon induction of the fusion protein. In addition to Hoxa9 and Meis1, this includes Eya1 and Six1 which comprise a heterodimeric transcription factor important in several developmental pathways. We show that Eya1 has the capacity to immortalize hematopoietic progenitor cells in vitro and collaborates with Six1 in hematopoietic transformation assays. Altogether, our data suggest that MLL fusions contribute to the development of acute leukemia through direct activation of a small set of target genes. We explored an inducible MLL-ENL cellular model, which was obtained from Dr. Robert Slany (University Erlangen, Germany). We wished to examine the differential expressed genes that are bound by MLL wild type (No 4-OHT) and fusion (4-OHT) proteins, combinding the ChIP-chip data to explore the potential MLL fusion-regulated genes.

2011-04-28 | E-GEOD-24794 | biostudies-arrayexpress

Remodelling of the DNA methylation landscape of leukemic cells upon FOSL2 KO or CD34 + cells upon CRISPR mediated t(4:11) rearrangement

Project description:In this dataset we used the most recent Illumina MethylationEPIC Beadchip platform to describe the genome-wide DNA methylation changes observed upon FOSL2 KO in SEM leukemia cells. In addition, we explored the DNA methylation effect of t(4:11) translocation in the context of CD34+ cells. These samples correspond to additional experimental work from the manuscript and are related to the ArrayExpress entry E-MTAB-8505.

2021-03-12 | E-MTAB-10090 | biostudies-arrayexpress

Comparison of miRNA expression profiling in CD14+ monocytes between anti-MDA5-positive three patients and three healthy controls

Project description:miRNA array was conducted to identify relevant pathological pathways in activated monocytes in anti-MDA5-positive patients in comparison of those in healthy controls.

2021-05-03 | E-MTAB-10471 | biostudies-arrayexpress

Transcription profiling of human dendritic cells after infection with A. fumigatus

Project description:DCs are localized under the mucosa of the lungs and the gastrointestinal tract, and therefore come into close contact with A. fumigatus germ tubes during early steps of infection as soon as fungi become invasive. For a more detailed insight into differentially regulated genes, whole genome microarray analysis was performed. On average, unstimulated DCs showed expression of about 13.500 genes (35% of all genes spotted on the chip). After 6h co-cultivation of DCs and live A. fumigatus germ tubes, 590 genes showed a 4fold altered gene expression, if normalizing data with VSN before. Therein, a wide range of immune response genes, including genes encoding for cytokines (IL-1Î±, IL-1Î², IL-6, IL-8, IL-10, IL-12p40, TNF-Î±), chemokines (CCL5, CCL20, CXCL10), immunorelevant receptors (TLR2, TLR4, PTX-3), as well as costimulatory molecules (CD40, CD80, CD83, CD86) were differentially regulated. Experiment Overall Design: Human DCs were generated from two independent, healthy blood donors. 5 x 106 DCs were either cultivated without fungi or together with 5 x 106 A. fumigatus germ tubes for 6h until isolation of total RNA.

2008-06-15 | E-GEOD-6965 | biostudies-arrayexpress

Comparison of gene microarray analysis in CD14+ monocytes between anti-MDA5-positive three patients and three healthy controls

Project description:mRNA array was conducted to identify relevant pathological pathways in activated monocytes in anti-MDA5-positive patients in comparison of those in healthy controls.

2021-05-04 | E-MTAB-10472 | biostudies-arrayexpress

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