RUNX2 gene expression from proximal (P2) promoter is stimulated by ESR1:estrogen, ESRRA:PPARG1CA, TWIST1 and RUNX2-P2, and inhibited by ESRRA:PPARG1CB and DEXA:NR3C1

Stable Identifier
R-HSA-8939900
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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RUNX2 gene expression from proximal (P2) promoter is stimulated by ESR1:estrogen, ESRRA:PPARG1CA, TWIST1 and RUNX2-P2, and inhibited by ESRRA:PPARG1CB and DEXA:NR3C1
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Activated estrogen receptor alpha (ESR1) directly stimulates the RUNX2 gene transcription by binding to estrogen response elements in the proximal P2 promoter of RUNX2. Estrogen-related receptor alpha (ESRRA) binds to estrogen response elements (EREs) or estrogen-related response elements (ERREs) in the proximal P2 promoter of the RUNX2 gene. In the presence of its PPARG1CA co-factor, ESRRA stimulates RUNX2 transcription. In the presence of another co-factor, PPARG1CB, ESRRA inhibits RUNX2 transcription (Kammerer et al. 2013).
Transcription of RUNX2 is stimulated by binding of TWIST1 transcription factor to the E1-box in the proximal P2 promoter of RUNX2 (Yang et al. 2011).
Studies in mice have shown that RUNX2-P2 can autoactivate its own expression by binding to the proximal P2 promoter of the RUNX2 gene (Ducy et al. 1999).

Based on studies in mice, transcription of RUNX2 from the proximal promoter is inhibited by binding of the glucocorticoid receptor (NR3C1) activated by dexamethasone (DEXA) to a glucocorticoid receptor response element (GRE), which is also present in the human promoter (Zhang et al. 2012). The complex of DEXA and NR3C1 may also inhibit RUNX2 activity by directly binding to the RUNX2 protein (Koromila et al. 2013).

Literature References
PubMed ID Title Journal Year
22422618 Down-regulation of type I Runx2 mediated by dexamethasone is required for 3T3-L1 adipogenesis

Zhang, YY, Li, X, Qian, SW, Guo, L, Huang, HY, He, Q, Liu, Y, Ma, CG, Tang, QQ

Mol. Endocrinol. 2012
21931630 Hypoxia inhibits osteogenesis in human mesenchymal stem cells through direct regulation of RUNX2 by TWIST

Yang, DC, Yang, MH, Tsai, CC, Huang, TF, Chen, YH, Hung, SC

PLoS ONE 2011
23943595 Glucocorticoids antagonize RUNX2 during osteoblast differentiation in cultures of ST2 pluripotent mesenchymal cells

Koromila, T, Baniwal, SK, Song, YS, Martin, A, Xiong, J, Frenkel, B

J. Cell. Biochem. 2014
10215629 A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

Ducy, P, Starbuck, M, Priemel, M, Shen, J, Pinero, G, Geoffroy, V, Amling, M, Karsenty, G

Genes Dev. 1999
23403054 Estrogen Receptor α (ERα) and Estrogen Related Receptor α (ERRα) are both transcriptional regulators of the Runx2-I isoform

Kammerer, M, Gutzwiller, S, Stauffer, D, Delhon, I, Seltenmeyer, Y, Fournier, B

Mol. Cell. Endocrinol. 2013
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
Glucocorticoid ligand:NR3C1:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
NR3C1:(ALDO,11DCORST,CORST,CORT) dimer [nucleoplasm]
Regulator
ESRRA:PPARG1CB:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
ESRRA:PPARGC1B [nucleoplasm]
Positively by
Regulator
RUNX2-P2:CBFB:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
RUNX2-P2:CBFB [nucleoplasm]
Regulator
TWIST1:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
TWIST1 [nucleoplasm]
Regulator
ESRRA:PPARG1CA:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
ESRRA:PPARGC1A [nucleoplasm]
Regulator
ESR1:estrogen:RUNX2 gene [nucleoplasm] (Homo sapiens)
Active Unit
ESR1 dimer:ESTG [nucleoplasm]
Inferred From
Runx2 gene expression from proximal (P2) promoter is stimulated by Runx2-P2 and inhibited by DEXA:Nr3c1 (Mus musculus)
Authored
Orlic-Milacic, M  (2016-09-21)
Reviewed
Ducy, P  (2017-08-04)
Created
Orlic-Milacic, M  (2016-09-21)
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