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MLL2, but not MLL1, plays a major role to sustain leukemia survival [RNA-seq]

ABSTRACT: We investigated the effect of Mll1, Mll2 and Mll1;Mll2 deletion on gene expression in MLL-AF9-transformed cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE93622 | GEO | 2017/01/20

SECONDARY ACCESSION(S): PRJNA362637

REPOSITORIES: GEO

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MLL2, but not MLL1, plays a major role to sustain leukemia survival [array]

Project description:The MLL1 histone methyltransferase gene undergoes many distinct chromosomal rearrangements to yield poor-prognosis leukemia. The remaining wild-type allele is most commonly, but not always, retained. To what extent the wild-type allele contributes to leukemogenesis is unclear. Here we show using rigorous, independent animal models that endogenous MLL1 is dispensable for MLL-rearranged leukemia. Potential redundancy was addressed by co-deleting the closest paralog, Mll2. Surprisingly, Mll2 deletion alone had a significant impact on survival of MLL-AF9-transformed cells and additional Mll1 loss further reduced viability and proliferation. We show that MLL1/MLL2 collaboration is not through redundancy but regulation of distinct pathways. These findings highlight the relevance of MLL2 as a drug target in MLL-rearranged leukemia and suggest its broader significance in AML. We used microarray to investigate the effect of Mll1 deletion on gene expression in LSC-enriched MLL-AF9 leukemia cells.

2017-01-20 | GSE93621 | GEO

MLL2, but not MLL1, plays a major role to sustain leukemia survival

Project description:MLL2, but not MLL1, plays a major role to sustain leukemia survival

| PRJNA362633 | ENA

MLL2, but not MLL1, plays a major role to sustain leukemia survival

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-20 | GSE93623 | GEO

MLL1 and MLL2 in vitro ChIP-Sequencing data [MLL1_MLL2_PA_VDH15]

Project description:MLL1 and MLL2 profiling of OSCC cells following in vitro exposure to palmitic acid (PA) for 4 days and after 14 days of palmitic acid withdrawal.

2021-11-16 | GSE149048 | GEO

ChipSeq of MLL1 in mouse leukemic blast cells

Project description:We performed a chip-seq to determine the binding of MLL1 in mouse leukemic blast cells transduces with MLL-AF9 fusion MLL1 chip-seq in mouse leukemic blast cells

2012-02-22 | E-GEOD-34261 | biostudies-arrayexpress

ChipSeq of MLL1 in mouse leukemic blast cells

Project description:We performed a chip-seq to determine the binding of MLL1 in mouse leukemic blast cells transduces with MLL-AF9 fusion

2012-02-22 | GSE34261 | GEO

Analysis of genome-wide occupancy of menin, MLL1 and MLL2 in MCF-7 cells

Project description:We performed ChIP-seq using antibodies directed at menin, MLL1 and MLL2 in MCF-7 cells in order to assess the genome-wide presence of these proteins in MCF-7 cells.

2017-03-09 | GSE85317 | GEO

MLL1 and MLL2 in vitro ChIP-Sequencing data [MLL1_MLL2_PA_VDH15]

Project description:MLL1 and MLL2 in vitro ChIP-Sequencing data [MLL1_MLL2_PA_VDH15]

| PRJNA627204 | ENA

Proteolytic cleavage by taspase1 and the regulation of the stability of MLL1

Project description:Chromosomal translocations of the Mixed-lineage leukemia 1 (MLL1) gene generate MLL-chimeras that drive pathogenesis of acute myeloid and lymphoid leukemia. The untranslocated MLL1 is a substrate for proteolytic cleavage by the endopeptidase, taspase1, however, the biological significance of MLL1 cleavage by this endopeptidase remains unclear. Here, we demonstrate that taspase1-dependent cleavage of MLL1 results in the destabilization of full-length MLL. Upon loss of taspase1, MLL1 association with chromatin is markedly increased due to the stabilization of its unprocessed version and this stabilization of the uncleaved MLL1 can result in the displacement of MLL-chimeras from chromatin in leukemic cells. Casein kinase II (CKII) phosphorylates MLL1 proximal to the taspase1 cleavage site, facilitating its cleavage, and pharmacological inhibition of CKII blocks taspase1-dependent MLL1 processing, increases MLL1 stability, and results in the displacement of the MLL-chimeras from chromatin. Furthermore, inhibition of CKII in MLL-AF9 mouse model of leukemia delayed leukemic progression in vivo. This study provides insights into the direct regulation of the stability of MLL1, which can be harnessed for targeted therapeutic approaches for the treatment of aggressive MLL leukemia.

2019-01-02 | GSE90762 | GEO

Expression analysis on Mll1+/+ and Mll1-/- MEFs

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

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