Meis1 genomics
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB50012 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7987050.fastq.gz | Fastqsanger.gz | |||
| ERR7987041.fastq.gz | Fastqsanger.gz | |||
| ERR7987051.fastq.gz | Fastqsanger.gz | |||
| ERR7987042.fastq.gz | Fastqsanger.gz | |||
| ERR7987052.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Meis1 is found cooperatively activated with Hoxa7/a9 in AML, and it indeed promotes leukemogenic activities of Hoxa9. It is important to identify downstream target genes of Meis1 to understand its cooperative activity with Hoxa9 in leukemogenesis. We used microarrays to detail the global programme of gene expression upon Meis1 knockout.
2015-01-01 | GSE50645 | GEO
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX proteins, such as HOXA9, to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. To further resolve these mechanisms, we conducted a structure-function analysis of Meis1 and miRNA expression profiling, in the context of Hoxa9 leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the homeodomain of Meis1 is required for leukemogenic collaboration with Hoxa9. miRNA expression profiling of a Hoxa9 preleukemic cell line transduced with wild-type or Meis1 homeodomain mutant reveal deregulation of multiple miRNA including a set not previously implicated as Meis1 targets.
2017-04-27 | GSE74566 | GEO
Project description:Meis1 is found cooperatively activated with Hoxa7/a9 in AML, and it indeed promotes leukemogenic activities of Hoxa9. It is important to identify downstream target genes of Meis1 to understand its cooperative activity with Hoxa9 in leukemogenesis. We used microarrays to detail the global programme of gene expression upon Meis1 knockout. Murine primary bone marrow cells of the Rosa26-Cre-ERT2 knock-in mouse were transformed by retroviral transduction of Hoxa9 and floxed Meis1. The immortalized bone marrow cells were treated with 2 μM of 4-hydroxytamoxifen to delete Meis1 cDNA. Gene expression profiles were compared between the original Hoxa9/Meis1-expressing cells and Meis1 deleted (Hoxa9 only) cells.
2015-01-01 | E-GEOD-50645 | biostudies-arrayexpress
Project description:The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feed-forward loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, we show that Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
2017-06-14 | PXD004192 | Pride
Project description:We have searched genome-wide binding sites of homeodomain proteins important for leukemogenesis in Hoxa9- and Meis1- induced myeloid leukemia cells. Thousands of binding sites of these three family proteins have been identified and many of them are co-localized with those of each others. Hoxa9 and Pbx binding sites were compared between the presence and absence of Meis1 by its knockout in the same cells. In combination of the results with gene expression profiles of the same cells, important downstream target genes of Meis1 in leukemogenesis have been identified.
2016-03-05 | GSE48679 | GEO
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX proteins, such as HOXA9, to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. To further resolve these mechanisms, we conducted a structure-function analysis of Meis1 and gene expression profiling, in the context of Hoxa9 leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the homeodomain of Meis1 is required for leukemogenic collaboration with Hoxa9. Gene expression profiling of a Hoxa9 preleukemic cell line transduced with wild-type or Meis1 homeodomain mutant reveal deregulation of multiple genes including a set not previously implicated as Meis1 targets.
2016-09-01 | GSE75272 | GEO
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX and NUP98-HOX fusion proteins to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. MATERIALS AND METHODS: To further resolve these mechanisms, we conducted a structure-function analysis of MEIS1 and gene-expression profiling, in the context of NUP98-HOXD13 (ND13) leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the PBX-interaction domain, the homeodomain, and the C-terminal domain of MEIS1, are all required for leukemogenic collaboration with ND13. In contrast, the N-terminal domain of MEIS1 is dispensable for collaboration with ND13, but is required for Flt3 upregulation, indicating additional roles for MEIS1 in induction of leukemia independent of alterations in Flt3 expression. Gene-expression profiling of a cloned ND13 preleukemic cell line transduced with wild-type or Meis1 mutant forms revealed deregulation of multiple genes, including a set not previously implicated as MEIS1 targets. Chromatin immunoprecipitation revealed the in vivo occupancy of MEIS1 on regulatory sequences of Trib2, Flt3, Dlk1, Ccl3, Ccl4, Pf4, and Rgs1. Furthermore, engineered overexpression of Trib2 complements ND13 to induce AML while Ccl3 potentiates the repopulating ability of ND13. CONCLUSION: This study shows that Meis1-induced leukemogenesis with ND13 can occur in the absence of Flt3 upregulation and reveals the existence of other pathways activated by MEIS1 to promote leukemia.
2009-04-09 | GSE15541 | GEO
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX proteins, such as HOXA9, to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. To further resolve these mechanisms, we conducted a structure-function analysis of Meis1 and gene expression profiling, in the context of Hoxa9 leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the homeodomain of Meis1 is required for leukemogenic collaboration with Hoxa9. Gene expression profiling of a Hoxa9 preleukemic cell line transduced with wild-type or Meis1 homeodomain mutant reveal deregulation of multiple genes including a set not previously implicated as Meis1 targets. Murine bone marrow cells transduced with Hoxa9-GFP + empty MIY vector were compared to Hoxa9+Meis1 cells or Hoxa9+Meis1 with deleted homeodomain (DHD) cells and cultured for three or four weeks before harvest for miRNA expression array. Four independent experiments were performed for each of the three different conditions included in the study. Cells from all samples were also transplanted into lethally irradiated mice to test for their transforming and leukemic potential.
2016-09-01 | E-GEOD-75272 | biostudies-arrayexpress
Project description:OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX and NUP98-HOX fusion proteins to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. MATERIALS AND METHODS: To further resolve these mechanisms, we conducted a structure-function analysis of MEIS1 and gene-expression profiling, in the context of NUP98-HOXD13 (ND13) leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the PBX-interaction domain, the homeodomain, and the C-terminal domain of MEIS1, are all required for leukemogenic collaboration with ND13. In contrast, the N-terminal domain of MEIS1 is dispensable for collaboration with ND13, but is required for Flt3 upregulation, indicating additional roles for MEIS1 in induction of leukemia independent of alterations in Flt3 expression. Gene-expression profiling of a cloned ND13 preleukemic cell line transduced with wild-type or Meis1 mutant forms revealed deregulation of multiple genes, including a set not previously implicated as MEIS1 targets. Chromatin immunoprecipitation revealed the in vivo occupancy of MEIS1 on regulatory sequences of Trib2, Flt3, Dlk1, Ccl3, Ccl4, Pf4, and Rgs1. Furthermore, engineered overexpression of Trib2 complements ND13 to induce AML while Ccl3 potentiates the repopulating ability of ND13. CONCLUSION: This study shows that Meis1-induced leukemogenesis with ND13 can occur in the absence of Flt3 upregulation and reveals the existence of other pathways activated by MEIS1 to promote leukemia. Establishment of pre-leukemic bone marrow cell lines following transduction with ND13 have been previously described (Pineault, Abramovich et al. 2005). In brief, lines were established from BM cells previously treated with 5-fluorouracil (5-FU) from (C57Bl/6Ly-Pep3b x C3H/HeJ) F1 (PepC3) (Ly5.1+/Ly5.2+) mice freshly transduced with the ND13-GFP or ND13pac virus and maintained in liquid culture. To generate ND13+Meis1 or ND13+Meis1 mutant BM cell lines, the ND13 BM cells were transduced by co-cultivation on irradiated (4,000 cGy) E86 producers for Meis1-YFP (or Meis1 mutant forms), respectively, for a period of 2 days in the presence of 5 µg/ml of protamine sulfate. Three independent experiments were performed for each of the four different conditions included in the study.
2009-04-09 | E-GEOD-15541 | biostudies-arrayexpress
Project description:Aberrant expression of homeobox transcription factor HOXA9 is a central component of the leukemogenic program driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid progenitor cells and pro-B cells leads to significant rearrangement of the epigenetic landscape with prominent emergence of cancer specific de novo enhancers. HOXA9 acts as a pioneer factor at the de novo enhancers and is required for recruitment of transcription factor CEBP/a and the histone H3K4 methyltransferase MLL3/MLL4 complex. HOXA9 function at the de novo enhancer is distinct from its physiological role at distal enhancers during normal hematopoietic development. Genetic deletion of MLL3/4 specifically affects the active enhancer signatures at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis. Our study reveals a previously uncharacterized role of HOXA9 and the MLL3/4 complex in leukemogenesis and provide mechanistic insights in epigenetic deregulation during malignant transformation.
2018-09-05 | GSE103447 | GEO