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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
nucleoplasm
,
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Gene expression (Transcription) (Homo sapiens)
RNA Polymerase II Transcription (Homo sapiens)
Generic Transcription Pathway (Homo sapiens)
Transcriptional regulation by RUNX1 (Homo sapiens)
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (Homo sapiens)
GP1BA gene transcription is stimulated by the complex containing RUNX1, PRMT1 and GATA1 and inhibited by the complex of RUNX1, SIN3A and PRMT6 (Homo sapiens)
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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
Participants
Input
GP1BA gene [nucleoplasm]
(Homo sapiens)
Output
GP1BA [plasma membrane]
(Homo sapiens)
Participates
as an event of
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (Homo sapiens)
This event is regulated
Negatively by
Regulator
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2,H3R2me2a-Nucleosome [nucleoplasm]
(Homo sapiens)
Active Unit
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1 [nucleoplasm]
Positively by
Regulator
H3K4me3-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2B [nucleoplasm]
(Homo sapiens)
Active Unit
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2B [nucleoplasm]
Authored
Orlic-Milacic, M (2016-09-14)
Reviewed
Chuang, LS (2016-12-20)
Ito, Y (2016-12-20)
Created
Orlic-Milacic, M (2016-08-22)
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