Ablation of MYB-dependent leukaemia phenotype in MLL-driven AML correlates with increased expression of MAFB
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA629123 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11638437_1.fastq.gz | Fastqsanger.gz | |||
| SRR11638437_2.fastq.gz | Fastqsanger.gz | |||
| SRR11638438_1.fastq.gz | Fastqsanger.gz | |||
| SRR11638438_2.fastq.gz | Fastqsanger.gz | |||
| SRR11638439_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:The transcription factor MYB plays a pivotal role in haematopoietic homeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). Our previous work on CEBPA mutants has demonstrated that not all AML types display the same dependency on MYB expression, rather this depends on the nature of the driving mutations. However, whether this difference in MYB expression dependency is a general trend in AML still remains to be further elucidated. In this study, we investigate the importance of MYB in human leukaemia by performing siRNA-mediated knock-down in cell lines modelling AML driven by different genetic lesions. We show that the reduction in proliferation and the concomitant induction of myeloid commitment observed in MLL-driven leukaemia upon suppression of MYB expression is not seen in AML cells with a complex karyotype. By performing transcriptome analysis, we demonstrate that reduction of MYB in the cell line that responds to its manipulation leads to a strong activation of MAFB expression. Correlating with these observations, stratification of publicly available patient data reveals a reciprocal relationship between the expression of MYB and MAFB, highlighting a novel connection between those two factors in such AML.
2023-04-29 | GSE149556 | GEO
Project description:MafA and MafB transcription factors have been shown to be key regulators of insulin and glucagon transcription. MafB is essential for alpha and beta cell differentiation, as MafB deficient mice produced fewer insulin+ and glucagon+ cells during development, with MafA expressed in remaining insulin+ cells. In contrast, beta cell development was reported to be normal in a total MafA knock out, although the animals developed beta cell dysfunction and diabetes as adults. However, we have found that MafB expression is elevated during development and retained in adult insulin+ cells after conditional removal of MafA in the pancreas. These studies will evaluate the broader significance of these insulin and glucagon regulators in alpha and beta cell development and function. Our efforts will focus on determining if the concerted actions of MafA and MafB factors are significant to beta cell formation, and we specifically plan to: Determine how alpha and beta cell differentiation is affected in MafA/MafB compound mutant mice during pancreas development. cDNA microarray studies (pancchip 6.0) with wild type, MafAKO, MafB-/-, and MafAKOMafB-/- mutant E18.5 pancreata will be performed to comprehensively identify genes controlled by MafA and MafB in developing alpha and beta cells.
2014-11-04 | E-MTAB-3070 | biostudies-arrayexpress
Project description:Mutations altering the normal function of C/EBPα are frequent in acute myeloid leukaemia with normal karyotype. MYB, a cooperating partner of C/EBPα, is likewise heavily implicated in AML. Here we investigate how the relative requirement for the transcription factor MYB in AML relates to the particular combinations of wild type and mutated alleles of CEBPA. Through knockdown of Myb in murine cell lines modelling the spectrum of CEBPA mutations we show that the consequences of reduced Myb depend on the mutational status of Cebpa. Importantly, Myb knockdown fails to override the block in myeloid differentiation in cells with biallelic N-terminal C/EBPα mutations, demonstrating for the first time that the dependency on Myb observed in AML is much lower in leukaemia with this combination of mutations. By comparing genome-wide analyses of gene expression following Myb knockdown and ChIP-seq data for the binding of C/EBPα isoforms, we provide evidence for a functional cooperation between C/EBPα and Myb in the maintenance of the leukaemia state. This co-dependency breaks down when both alleles of CEBPA harbour N-terminal mutations, as a subset of C/EBPα-regulated genes only bind the short p30 C/EBPα isoform and, unlike other C/EBPα regulated genes, do so without a requirement for Myb.
2019-03-13 | GSE119348 | GEO
Project description:IMMUNE CORRELATES OF RESPONSE TO IMMUNE CHECKPOINT BLOCKADE IN ACUTE MYELOID LEUKAEMIA
| PRJNA741507 | ENA
Project description:Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks and altered biological pathways. We further investigated the secreted proteins for their potential biomarker properties.
2021-09-08 | PXD015126 | Pride
Project description:Most E2F-binding sites repress transcription through the recruitment of Retinoblasoma (RB) family members until the end of the G1 cell-cycle phase. Although the MYB promoter contains an E2F-binding site, its transcription is activated shortly after the exit from quiescence, before RB family members inactivation, by unknown mechanisms. We had previously uncovered a nuclear factor distinct from E2F, Myb-sp, whose DNA-binding site overlapped the E2F element and had hypothesized that this factor might overcome the transcriptional repression of MYB by E2F-RB family members. We have purified Myb-sp and discovered that Myc-associated zinc finger proteins (MAZ) are major components. We show that various MAZ isoforms are present in Myb-sp and activate transcription via the MYB-E2F element. Moreover, while forced RB or p130 expression repressed the activity of a luciferase reporter driven by the MYB-E2F element, co-expression of MAZ proteins not only reverted repression, but also activated transcription. Finally, we show that MAZ binds the MYB promoter in vivo, that its binding site is critical for MYB transactivation, and that MAZ knockdown inhibits MYB expression during the exit from quiescence. Together, these data indicate that MAZ is essential to bypass MYB promoter repression by RB family members and to induce MYB expression.
2017-10-04 | PXD006857 | Pride
Project description:The intent of this experiment was to determine MAFB binding sites in human pancreatic beta cells. This is particularly relevant as MAFB is not expressed in mature rodent beta cells; thus, it may perform unique functions in human. Sequencing was performed following IP with an anti-MAFB antibody using chromatin isolated from the human pancreatic beta cell line, EndoCBH2 cells. Cells were proliferating and untreated when collected.
2020-03-17 | E-MTAB-8612 | biostudies-arrayexpress
Project description:MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains.Although it is well known that MafB is specifically expressed in macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages. To investigate detail function of MafB in nonadherent macrophages, we performed microarray analysis. Macrophages were derived from day 14.5 fetal livers of mafB- /- and WT mice. Suspensions of single fetal liver cells were prepared by mechanical disruption . A total of 106 cells in suspension were centrifuged at 1,200 rpm for 5 min, and the cell pellet was resuspended in Dulbeccoâs modified Eagleâs medium supplemented with 10% fetal calf serum (heat inactivated), streptomycin and penicillin (100 units/ml), and macrophage colony-stimulating factor (M-CSF) (10 ng/ml) and then seeded either onto a nonadhesive dishes coated with hydrophilic polymers (Hydrocell; Cell Seed, Tokyo). The culture medium was not changed throughout the experiment. M-CSF (final concentration, 10 ng/ml) was added every day from day 4 onwards. One, 2, 4, and 6 days after seeding, the cells were harvested and analyzed by flow cytometry. After 6 day culture, macrophages of Mafb-/- and WT were use microarray analysis .
2010-02-27 | E-GEOD-20419 | biostudies-arrayexpress
Project description:The transcription factor MafB is essential for differentiation and foot process formation of podocytes. In order to identify the downstream targets of MafB, we analyzed the Mafb-deficient podocyte by RNA-seq. We found slit diaphragm-related protein (Nphs1, Magi2), Rho GTPase-activating protein (Arhgap24, Iqgap2) and podocyte-specific transcription factor (Tcf21) were significantly reduced in MafB cKO glomeruli. This indicates that one of these factors might be directly regulated by MafB to maintain its function in podocyte maintenance.
2021-08-03 | GSE96044 | GEO
Project description:MafB is a transcription factor acts as an important regulator of the development and differentiation of various organs and tissues. MafB is expressed in sertoli, leydig, and germ cells in adult mice testis. However, analysis of MafB cKO mice testis showed that MAFB is required for the initiation of the first spermatogenic wave but not the subsequent waves. We examined the transcriptome profile of MafB-cKO Sertoli cells during the first spermatogenic wave. Results of the down-regulated genes revealed that some genes are direct targets of MAFB since the presence of MARE sites in their promoters. Thus, they are candidates of maintaining MAFB function in sertoli cells.
2023-12-21 | GSE94725 | GEO