Pathway
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
In human hematopoietic progenitors, RUNX1 and its partner CBFB are up-regulated at the onset of megakaryocytic differentiation and down-regulated at the onset of erythroid differentiation. The complex of RUNX1 and CBFB cooperates with the transcription factor GATA1 in the transactivation of megakaryocyte-specific genes. In addition, RUNX1 and GATA1 physically interact, and this interaction involves the zinc finger domain of GATA1. Other components of the RUNX1:CBFB activating complex at megakaryocytic promoters are GATA1 heterodimerization partner, ZFPM1 (FOG1), histone acetyltransferases EP300 (p300) and KAT2B (PCAF), the WDR5-containing histone methyltransferase MLL complex and the arginine methyltransferase PRMT1. In the absence of PRMT1, the transcriptional repressor complex can form at megakaryocytic promoters, as RUNX1 that is not arginine methylated can bind to SIN3A/SIN3B co-repressors. Besides SIN3A/SIN3B, the RUNX1:CBFB repressor complex at megakaryocytic promoters also includes histone deacetylase HDAC1 and histone arginine methyltransferase PRMT6.
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Megakaryocytic promoters regulated by the described RUNX1:CBFB activating and repressing complexes include ITGA2B, GP1BA, THBS1 and MIR27A. ITGA2B is only expressed in maturing megakaryocytes and platelets and is involved in platelet aggregation. GP1BA is expressed at the cell surface membrane of maturing megakaryocytes and platelets and participates in formation of platelet plugs. THBS1 homotrimers contribute to stabilization of the platelet aggregate. MIR27A is a negative regulator of RUNX1 mRNA translation and may be involved in erythroid/megakaryocytic lineage determination.
The RUNX1:CBFB complex stimulates transcription of the PF4 gene, encoding a component of platelet alpha granules, the NR4A3 gene, associated with the familial platelet disorder (FPD), the PRKCQ gene, associated with inherited thrombocytopenia, the MYL9 gene, involved in thrombopoiesis, and the NFE2 gene, a regulator of erythroid and megakaryocytic maturation and differentiation.
What the reference databases state
Statements
62 statements
62 statements · 1 reference database · Subject: RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function · Sources: Reactome
- AGO1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- AGO3 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- AGO4 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- ASH2L participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- CBFB participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- DPY30 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- EP300 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- GATA1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- GP1BA participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AB1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AC14 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AC18; H2AC19 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
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- H2AC20 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AC4; H2AC8 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AC6 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AC7 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AJ participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AX participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2AZ2 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC11 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC12 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC13 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC14 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC15 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC17 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC21 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC26 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC3 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC4; H2BC6; H2BC7; H2BC8; H2BC10 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H2BC9 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H3-3A; H3-3B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H3C15; H3C14; H3C13 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- H4C1; H4C2; H4C3; H4C4; H4C5; H4C6; H4C8; H4C9; H4C11; H4C12; H4C13; H4C14; H4C15; H4C16 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- HDAC1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- ITGA2B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- KAT2B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- KMT2A participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- KMT2B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- KMT2C participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- KMT2D participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- MOV10 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- MYL9 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- NFE2 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- NR4A3 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- PF4 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- PRKCQ participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- PRMT1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- PRMT6 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- RBBP5 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- RUNX1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- SETD1A participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- SETD1B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- SIN3A participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- SIN3B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- THBS1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- TNRC6A participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- TNRC6B participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- TNRC6C participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- WDR5 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only
- ZFPM1 participates in RUNX1 regulates genes involved in megakaryocyte differentiation and platelet functionProteinReactome R-HSA-8936459Inferred only