RUNX2 gene expression from distal (P1) promoter is inhibited by NKX3-2, MSX2 and RUNX2-P1, and stimulated by DLX5,(DLX6)

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
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
Based on studies in mice, RUNX2 transcription is repressed by binding of the transcriptional repressor NKX3-2 (BAPX1) to the distal (P1) RUNX2 gene promoter (Lengner et al. 2005, Provot et al. 2006). RUNX2 itself can autoregulate through a negative feedback mechanism by binding of the RUNX2-P1 isoform to the evolutionarily conserved RUNX2 response elements in the distal P1 promoter (Drissi et al. 2000).

Based on studies in mice, transcription of RUNX2 from the distal (P1) promoter is directly stimulated by DLX5 (and possibly DLX6). Binding of DLX5 to the RUNX2 promoter is antagonized by MSX2. Once bound to the RUNX2 promoter, MSX2 inhibits RUNX2 transcription (Lee et al. 2005). DLX5 is activated by BMP2 signaling through an unknown mechanism.
Transcription of RUNX2 from the P1 promoter may be inhibited by the transcriptional repressor GFI1, which is essential for hematopoiesis (D'Souza et al. 2011).

Literature References
PubMed ID Title Journal Year
12000792 The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development

Li, X, Robledo, RF, Rajan, L, Lufkin, T

Genes Dev. 2002
16115867 Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter

Choi, KY, Lee, MH, Cho, JY, Wozney, JM, Hwang, YS, Kim, YJ, Choi, JY, Bae, SC, Ryoo, HM, Chi, XZ, Kim, BG, Kim, JI, Yoon, WJ

J. Biol. Chem. 2005
10911365 Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene

Jones, S, Luc, Q, Stein, JL, Stein, GS, Choi, JY, Neil, JC, Hu, M, Van Wijnen, AJ, Terry, A, Drissi, H, Shakoori, R, Chuva De Sousa Lopes, S, Lian, JB

J. Cell. Physiol. 2000
15703179 Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation

van Wijnen, AJ, Lengner, CJ, Lian, JB, Stein, JL, Stein, GS, Lepper, C, Hassan, MQ, Serra, RW

J. Biol. Chem. 2005
16421188 Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation

Lassar, AB, Kim, DW, Kronenberg, HM, Kempf, H, Chyung, J, Murtaugh, LC, Chung, UI, Provot, S

Development 2006
This event is regulated
Inferred From
Cite Us!