Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA132361 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, SCL/TAL1 and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, SCL/TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-specific cis-regulatory modules in multipotential hematopoietic progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming occurs is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential precursor via overlapping and divergent functions of shared hematopoietic transcription factors. Gene expression changes during the development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells
2013-08-09 | E-GEOD-49664 | biostudies-arrayexpress
Project description:We have mapped the binding sites for the five key regulators GATA1, GATA2, RUNX1, FLI1 and TAL1/SCL in primary human megakaryocytes. Statistical analysis identified subsets of enriched as well as depleted combinatorial binding patterns. In particular simultaneous binding by all 5 factors was highly enriched and occurred in the vicinity of many genes known to be involved in blood and megakaryocyte development. Knock down in zebrafish of 8 of these genes with no previously known role in hematopoiesis, revealed all to be essential for thrombocyte and/or erythroid development. Combinatorial analysis of multi-factor ChIP-Seq datasets coupled with a high-throughput in vivo screen therefore offers a powerful strategy to identify novel essential regulators of complex mammalian differentiation processes. 5 transcription factors and rabbit-IgG in megakaryocytes.
2011-06-01 | E-GEOD-24674 | biostudies-arrayexpress
Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, SCL/TAL1 and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, SCL/TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-specific cis-regulatory modules in multipotential hematopoietic progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming occurs is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential precursor via overlapping and divergent functions of shared hematopoietic transcription factors.
2013-08-09 | GSE49664 | GEO
Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated cis-regulatory modules (CRMs) in multipotential progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential progenitor via overlapping and divergent functions of shared hematopoietic transcription factors. Genome-wide chromatin occupancy using ChIP-seq on 4 transcription factors (GATA1, GATA2, TAL1, and FLII) and three histone marks (H3K4me1, H3K4me3, and H3K27me3) in lineage-commited primary erythoblasts (ERY) and primary cultured megakaryocytes (MEG).
2014-11-14 | E-GEOD-51337 | biostudies-arrayexpress
Project description:We have mapped the binding sites for the five key regulators GATA1, GATA2, RUNX1, FLI1 and TAL1/SCL in primary human megakaryocytes. Statistical analysis identified subsets of enriched as well as depleted combinatorial binding patterns. In particular simultaneous binding by all 5 factors was highly enriched and occurred in the vicinity of many genes known to be involved in blood and megakaryocyte development. Knock down in zebrafish of 8 of these genes with no previously known role in hematopoiesis, revealed all to be essential for thrombocyte and/or erythroid development. Combinatorial analysis of multi-factor ChIP-Seq datasets coupled with a high-throughput in vivo screen therefore offers a powerful strategy to identify novel essential regulators of complex mammalian differentiation processes.
2011-06-01 | GSE24674 | GEO
Project description:The Stem Cell Leukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for normal megakaryopoiesis. However, unlike other members of this complex such as Gata1, Fli1 and Runx1, mutations of Scl have not been observed as a cause of inherited thrombocytopenia. We postulated that functional redundancy with its closely related family member, Lymphoblastic Leukemia 1 (Lyl1) might explain this observation. To determine if Lyl1 can substitute for Scl in megakaryopoiesis, we examined the platelet phenotype of mice lacking one or both factors in megakaryocytes. Conditional Scl knockout mice crossed with transgenic mice expressing Cre recombinase under the control of the mouse platelet factor 4 (Pf4) promoter generated megakaryocytes with markedly reduced but not absent Scl. These Pf4SclcKO mice had mild thrombocytopenia and subtle defects in platelet aggregation. However, Pf4SclcKO mice generated on a Lyl1-null background (double knockout, DKO mice) had severe macrothrombocytopenia, abnormal megakaryocyte morphology, defective pro-platelet formation and markedly impaired platelet aggregation. DKO megakaryocytes, but not single knockouts, had reduced expression of Gata1, Fli1, Nfe2 and many other genes that cause inherited thrombocytopenia. These gene expression changes were significantly associated with shared Scl and Lyl1 E-box binding sites that were also enriched for Gata1, Ets and Runx1 motifs. Thus, Scl and Lyl1 share functional roles in platelet production and function by regulating expression of partner proteins including Gata1 and Fli1. We propose that this functional redundancy provides one explanation for the absence of Scl and Lyl1 mutations as a cause of inherited thrombocytopenia.
2020-12-21 | GSE125025 | GEO
Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated cis-regulatory modules (CRMs) in multipotential progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential progenitor via overlapping and divergent functions of shared hematopoietic transcription factors.
2014-11-14 | GSE51337 | GEO
Project description:Combinatorial transcription factor (TF) interactions control cellular phenotypes and therefore underpin stem cell formation, maintenance and differentiation. Here we report the genome-wide binding patterns and combinatorial interactions for 10 key regulators of blood stem/progenitor cells (Scl/Tal1, Lyl1, Lmo2, Gata2, Runx1, Meis1, Pu.1, Erg, Fli-1, Gfi1b) thus providing the most comprehensive TF dataset for any adult stem/progenitor cell type to date. Genome-wide computational analysis of complex binding patterns followed by functional validation revealed the following: First, a previously unrecognized combinatorial interaction between a heptad of TFs (Scl, Lyl1, Lmo2, Gata2, Runx1, Erg, Fli-1). Second, we implicate direct protein-protein interactions between four key regulators (Runx1, Gata2, Scl, Erg) in stabilising complex binding to DNA. Third, Runx1+/-::Gata2+/- compound heterozygous mice are not viable with severe haematopoietic defects at midgestation. Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells.
2010-10-07 | GSE22178 | GEO
Project description:Combinatorial transcription factor (TF) interactions control cellular phenotypes and therefore underpin stem cell formation, maintenance and differentiation. Here we report the genome-wide binding patterns and combinatorial interactions for 10 key regulators of blood stem/progenitor cells (Scl/Tal1, Lyl1, Lmo2, Gata2, Runx1, Meis1, Pu.1, Erg, Fli-1, Gfi1b) thus providing the most comprehensive TF dataset for any adult stem/progenitor cell type to date. Genome-wide computational analysis of complex binding patterns followed by functional validation revealed the following: First, a previously unrecognized combinatorial interaction between a heptad of TFs (Scl, Lyl1, Lmo2, Gata2, Runx1, Erg, Fli-1). Second, we implicate direct protein-protein interactions between four key regulators (Runx1, Gata2, Scl, Erg) in stabilising complex binding to DNA. Third, Runx1+/-::Gata2+/- compound heterozygous mice are not viable with severe haematopoietic defects at midgestation. Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells. 10 Samples (9 Transcription Factors and 1 Histone Modification) and 1 Control (IgG). All from the same cell line, a haematopoietic progenitor cell line (HPC-7).
2010-10-07 | E-GEOD-22178 | biostudies-arrayexpress
Project description:Combinatorial transcription factor (TF) interactions regulate hematopoietic stem cell formation, maintenance and differentiation, and are increasingly recognised as drivers of stem cell signatures in cancer. However, genome-wide combinatorial binding patterns for key regulators do not exist in primary human hematopoietic stem/progenitor cells (HSPCs) and have constrained analysis of the global architecture of the molecular circuits controlling these cells. Here we provide new high-resolution genome-wide binding maps of seven key TFs (FLI1, ERG, GATA2, RUNX1, SCL, LYL1 and LMO2) in human CD34+ HSPCs together with quantitative RNA and microRNA expression profiles. We catalogue binding of TFs at coding genes and microRNA promoters and report that combinatorial binding of all seven TFs is favoured and is associated with differential expression of genes and microRNA in HSPCs. We also uncover a hitherto unrecognized association between FLI1 and RUNX1 pairing in HSPCs, establish a correlation between the density of histone modifications, which mark active enhancers and the number of overlapping TFs at a peak and identify complex relationships between specific miRNAs and coding genes regulated by the heptad. Taken together, this study demonstrates that a heptad of TFs forms a dense auto-regulatory core in human HSPCs with binding of all seven TFs at tissue specific regulatory elements of heptad genes and collectively regulates miRNAs that in turn target components of the heptad and genes regulated by the heptad. Examination of cominatorial binding by 7 transcription factors, 1 IgG control along with mRNA and small RNA sequencing in human CD34+ cells
2013-09-03 | E-GEOD-45144 | biostudies-arrayexpress