RUNX1:CBFB, SIN3A(SIN3B), PRMT6 and HDAC1 bind the THBS1 gene promoter

Stable Identifier
R-HSA-8936989
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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The transcriptional co-repressor SIN3A (and possibly SIN3B) can bind to the RUNX1:CBFB complex at the promoter of the THBS1 (TSP-1) gene, encoding Thrombospondin-1. Binding of SIN3A (and probably SIN3B) to RUNX1 is inhibited by PRMT1-mediated arginine methylation of RUNX1 arginine residues R206 and R210 (Zhao et al. 2008). In addition to SIN3A, the RUNX1-containing transcriptional repressor complex at the THBS1 promoter also includes histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1 (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte promoters prior to the onset of differentiation (Herglotz et al. 2013), and based on epigenetic modifications that affect transactivation of the THBS1 gene (Michaud-Levesque and Richard 2009), the H3K4me2 mark is assumed to be present at the inactive THBS1 promoter.
Literature References
PubMed ID Title Journal Year
19509293 Thrombospondin-1 is a transcriptional repression target of PRMT6

Michaud-Levesque, J, Richard, S

J. Biol. Chem. 2009
18316480 Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity

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

Genes Dev. 2008
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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