THBS1 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-8936995
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The RUNX1:CBFB complex binds the promoter of the THBS1 (TSP-1) gene, encoding Thrombospondin-1, and stimulates THBS1 transcription. Based on the analogy with the ITGA2B gene transcription, transcription of THBS1 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 THBS1 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 RUNX1-regulated megakaryocyte promoters (Herglotz et al. 2013). The presence of the H3K4me3 mark is characteristic of the activated THBS1 promoter (Michaud-Levesque and Richard 2009).
The transcription repressor complex at the THBS1 promoter is formed when 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 RUNX1-regulated megakaryocyte promoters (Herglotz et al. 2013), including THBS1 promoter (Michaud-Levesque and Richard 2009).
Thrombospondin-1, encoded by the THBS1 gene, forms homotrimers which can be detected in many different cell types and are very abundant in platelet alpha granules. While THBS1 is not necessary for platelet aggregation, it contributes to stabilization of the platelet aggregate (Bonnefoy and Hoylaerts 2008).

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
19509293 Thrombospondin-1 is a transcriptional repression target of PRMT6

Michaud-Levesque, J, Richard, S

J. Biol. Chem. 2009
Participants
Participant Of
This event is regulated
Authored
Reviewed
Created