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Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

ABSTRACT: Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

ORGANISM(S): Homo sapiens

PROVIDER: GSE24777 | GEO | 2011/01/10

SECONDARY ACCESSION(S): PRJNA133387

REPOSITORIES: GEO

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Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models

Project description:This SuperSeries is composed of the following subset Series: GSE24777: Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners GSE24778: Expresssion data in K562 cells, before and after TPA induction and including a RUNX1 knockout construct or a control structure Refer to individual Series

2011-01-10 | E-GEOD-24779 | biostudies-arrayexpress

Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

Project description:Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners Examination of RUNX1 binding in K562 cells, before and following TPA induction and CMK cells. Examination of GATA1 and FOS binding and H3K4me1 and H3K27me3 modification levels following TPA induction in K562 cells.

2011-01-10 | E-GEOD-24777 | biostudies-arrayexpress

Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models

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

2011-01-10 | GSE24779 | GEO

Project description:Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models

| PRJNA132223 | ENA

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (expression)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 and p300 identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif. The data provides the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK, unravels the Runx1-regulated program controlling MK maturation in vivo and identifies its bona fide regulated genes. It advances our understanding of the molecular events that upon mutations in RUNX1 lead to the predisposition to familial platelet disorders and FPD-AML.

2013-03-22 | GSE45373 | GEO

SON inhibits megakaryocytic differentiation via repressing the megakaryocytic gene expression program in acute megakaryoblastic leukemia

Project description:A high incidence of acute megakaryoblastic leukemia (AMKL) in Down syndrome patients implies that chromosome 21 genes have a pivotal role in AMKL development, but the functional contribution of individual genes remains elusive. Here, we report that SON, a chromosome 21-encoded DNA- and RNA-binding protein, inhibits megakaryocytic differentiation by suppressing RUNX1 and the megakaryocytic gene expression program. As megakaryocytic progenitors differentiate, SON expression is drastically reduced, with mature megakaryocytes having the lowest levels. In contrast, AMKL cells express an aberrantly high level of SON, and knockdown of SON induced the onset of megakaryocytic differentiation in AMKL cell lines. Genome-wide transcriptome analyses revealed that SON knockdown turns on the expression of pro-megakaryocytic genes while reducing erythroid gene expression. Mechanistically, SON represses RUNX1 expression by directly binding to the proximal promoter and two enhancer regions, the known +23 kb enhancer and the novel +139 kb enhancer, at the RUNX1 locus to suppress H3K4 methylation. In addition, SON represses the expression of the AP-1 complex subunits JUN, JUNB and FOSB which are required for late megakaryocytic gene expression. Our findings define SON as a negative regulator of RUNX1 and megakaryocytic differentiation, implicating SON overexpression in impaired differentiation during AMKL development.

2020-09-01 | GSE157178 | GEO

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (expression)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andÂ p300Â identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.Â The data providesÂ the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,Â unravels the Runx1-regulated program controlling MK maturationÂ in vivoÂ andÂ identifies itsÂ bona fideÂ regulated genes. It advances our understandingÂ of the molecular events that upon mutations in RUNX1 lead to theÂ predisposition to familial platelet disorders and FPD-AML. Gene expression profiles of mature megakaryocytes taken from fetal livers of megakaryocyte-specific Runx1 knockout mice, using Runx1F/F/Pf4-Cre mice versus control (WT) mice.

2013-03-22 | E-GEOD-45373 | biostudies-arrayexpress

Homo sapiens

Project description:Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

| PRJNA133387 | ENA

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (ChIP-seq)

2013-03-22 | GSE45372 | GEO

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (ChIP-seq)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andÂ p300Â identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.Â The data providesÂ the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,Â unravels the Runx1-regulated program controlling MK maturationÂ in vivoÂ andÂ identifies itsÂ bona fideÂ regulated genes. It advances our understandingÂ of the molecular events that upon mutations in RUNX1 lead to theÂ predisposition to familial platelet disorders and FPD-AML. Examination of RUNX1 and P300 binding in WT mouse megakaryoctye cells using ChIP-Seq. The supplementary 'GSE45372_PeakList.txt' file includes a list of regions identified as binding for P300 or RUNX1 or both.

2013-03-22 | E-GEOD-45372 | biostudies-arrayexpress

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