GP1BA gene transcription is stimulated by the complex containing RUNX1, PRMT1 and GATA1 and inhibited by the complex of RUNX1, SIN3A and PRMT6

Stable Identifier
R-HSA-8936628
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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The RUNX1:CBFB complex binds the promoter of the GP1BA (CD42b) gene, encoding Platelet glycoprotein Ib alpha chain, and stimulates GP1BA transcription. Based on analogy with the ITGA2B gene transcription, transcription of GP1BA 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 GP1BA gene 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 GP1BA gene promoter (Herglotz et al. 2013).
The transcription repressor complex at the GP1BA 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 GP1BA gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
Platelet glycoprotein Ib (GP-Ib) alpha chain, encoded by the GP1BA gene, is expressed at the cell surface membrane of platelets and participates in the formation of platelet plugs (Cauwenberghs et al. 2000, Jilma-Stohlawetz et al. 2003). Gp-Ib protein is first detected on the plasma membrane of maturing megakaryocytes (Debili et al. 1990).
Literature References
PubMed ID Title Journal Year
22777353 Histone arginine methylation keeps RUNX1 target genes in an intermediate state

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

Oncogene 2013
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