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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R-HSA-8939900
Type
Reaction [omitted]
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Homo sapiens
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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
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
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
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
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