ITGA2B gene transcription is stimulated by the complex of RUNX1, GATA1 and PRMT1 and inhibited by the complex of RUNX1, SIN3A and PRMT6

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R-HSA-8935731
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Reaction [omitted]
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Homo sapiens
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The RUNX1:CBFB complex binds the promoter of the ITGA2B (CD41) gene, encoding Integrin alpha IIb, and stimulates ITGFA2B transcription. Transcription of ITGA2B is significantly upregulated by PRMT1-dependent arginine methylation of RUNX1, which interferes with the recruitment of the SIN3A (or, possibly, SIN3B) co-repressor (Zhao et al. 2008). The transcription activator complex at the ITGA2B promoter includes the RUNX1:CBFB complex, PRMT1, the GATA1:ZFPM1 complex, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), and the WDR5-containing histone methyltransferase MLL complex. The MLL complex produces the activating H3K4me3 mark on nucleosomes associated with the ITGA2B gene promoter (Herglotz et al. 2013).
The transcription repressor complex at the ITGA2B promoter is formed when the SIN3A (or possibly SIN3B) co-repressor binds to the RUNX1:CBFB complex along with histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the ITGA2B gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
ITGA2B, involved in platelet aggregation, is only expressed in maturing megakaryocytes and platelets and is a model gene for megakaryocyte specific expression (Block and Poncz 1995, Jackson 2007).

Literature References
PubMed ID Title Journal Year
22777353 Histone arginine methylation keeps RUNX1 target genes in an intermediate state

Herglotz, J, Kuvardina, ON, Kolodziej, S, Kumar, A, Hussong, H, Grez, M, Lausen, J

Oncogene 2013
18316480 Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity

Zhao, X, Jankovic, V, Gural, A, Huang, G, Pardanani, A, Menendez, S, Zhang, J, Dunne, R, Xiao, A, Erdjument-Bromage, H, Allis, CD, Tempst, P, Nimer, SD

Genes Dev. 2008
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