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Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (HEL Cell Line Bulk mRNA-seq)

ABSTRACT: Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (HEL Cell Line Bulk mRNA-seq)

PROVIDER: PRJNA974362 | ENA |

REPOSITORIES: ENA

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Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (HEL Cell Line Bulk mRNA-seq)

Project description:The differentiation of primary human megakaryocyte-erythroid progenitors (MEP) into megakaryocytic (Mk) or erythroid (E) progenitors is critical for maintaining the blood system, yet the mechanisms that regulate this fate specification remain unclear. Here, we analyzed RNA-seq data and found that RUNX1 is a key regulator of differential gene expression in MEP fate specification. Through viral transduction of primary MEP with RUNX1, we demonstrated that overexpression of RUNX1 promotes Mk over E specification, whereas pan-RUNX inhibition promotes E fate specification over Mk. We found that although the levels of total RUNX1 do not differ between MkP and ErP, MkP have higher levels of RUNX1 phosphorylated serine residues, and that serine/threonine phosphorylation of RUNX1 dramatically increases its effectiveness. We used human erythroleukemia (HEL) cell lines with expression of HA-tagged WT RUNX1, phosphomimetic (RUNX1-4D) and non-phosphorylatable (RUNX1-4A) mutants to model their effects on MEP. Although the chromatin association was not informative, the three forms of RUNX1 caused differential expression of 2,625 genes. Approximately 40% of these differentially expressed genes (DEGs) showed an increase with both RUNX1-WT and RUNX1-4D while another 40% showed a decrease with both RUNX1-WT and RUNX1-4D. We compared these DEGs with DEGs from primary human MEP, Mk progenitors (MkP), and E progenitors (ErP), and found that the genes upregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes upregulated in MkP vs. MEP, whereas genes downregulated by WT and RUNX1-4D in HEL cells overlapped significantly with the genes downregulated in MkP vs. MEP. These results suggest that phosphorylation of RUNX1 enhances RUNX1’s function to activate or repress transcription of target genes that are up/downregulated during MEP fate specification.

2024-09-24 | GSE232878 | GEO

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors

Project description:Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors

| PRJNA974359 | ENA

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (CUT&RUN)

2024-09-24 | GSE232877 | GEO

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (Primary Human Bulk mRNA-seq)

2024-09-24 | GSE232879 | GEO

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (CUT&RUN)

Project description:Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (CUT&RUN)

| PRJNA974361 | ENA

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (Primary Human Bulk mRNA-seq)

Project description:Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors (Primary Human Bulk mRNA-seq)

| PRJNA974364 | ENA

MKL1 promotes megakaryocytic differentiation in HEL cells

Project description:Megakaryoblastic Leukemia 1 (MKL1) was identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, but nothing is known regarding its role in hematopoiesis. Here we show that overexpression of MKL1 enhances megakaryocytic differentiation of the Human Erythroleukemia cell line (HEL). Microarray analysis reveals that MKL1 promotes expression of megakaryocyte-specific genes such as glycoprotein V (GP5), as well as cytoskeletal and adhesion molecule genes relevant to megakaryocyte differentiation and proplatelet formation. MKL1 is a transcriptional coactivator of Serum Response Factor. In this study, MKL1 also upregulates known SRF targets. Results provide insight into the role of MKL1 in megakaryocytopoiesis.

2008-12-10 | GSE13710 | GEO

Transcription profiling of mouse NIH3T3 cells over-expressing RNA-dependent serine/threonine protein kinase (PKR)PKR

Project description:Global analysis of gene expression in NIH3T3 cells over-expressing RNA-dependent serine/threonine protein kinase (PKR).

2008-06-15 | E-GEOD-682 | biostudies-arrayexpress

SERINE/THREONINE-PROTEIN PHOSPHATASE7-LIKE PP7L Regulates Chloroplast Development

Project description:SERINE/THREONINE-PROTEIN PHOSPHATASE7-LIKE PP7L Regulates Chloroplast Development

| PRJNA505350 | ENA

Serine/Threonine Phosphorylation of RUNX1 Promotes Megakaryocytic Fate in Megakaryocyte-Erythroid Progenitors

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

2024-09-24 | GSE232880 | GEO