|ZFIN ID: ZDB-PUB-100317-12|
The transcription factor Snail regulates osteogenic differentiation by repressing Runx2 expression
Park, S.J., Jung, S.H., Jogeswar, G., Ryoo, H.M., Yook, J.I., Choi, H.S., Rhee, Y., Kim, C.H., and Lim, S.K.
|Source:||Bone 46(6): 1498-1507 (Journal)|
|Registered Authors:||Jung, Seung-Hyun, Kim, Cheol-Hee|
|Keywords:||Snail, Runx2, E-box, Osteogenic differentiation|
|PubMed:||20215006 Full text @ Bone|
Park, S.J., Jung, S.H., Jogeswar, G., Ryoo, H.M., Yook, J.I., Choi, H.S., Rhee, Y., Kim, C.H., and Lim, S.K. (2010) The transcription factor Snail regulates osteogenic differentiation by repressing Runx2 expression. Bone. 46(6):1498-1507.
ABSTRACTOsteoblasts originate from mesenchymal stem cells by the coordinated activities of different signaling pathways that regulate the expression of osteoblast-specific genes. Runt-related transcription factor 2 (Runx2) is the master transcription factor for osteoblast differentiation. Despite the importance of Runx2 in the developing skeleton, how Runx2 expression is regulated remains a pivotal question. Snail, a zinc-finger transcription factor, is essential for triggering epithelial-to-mesenchymal transitions (EMTs) during embryonic development and tumor progression. Here, we report that Runx2 expression is significantly up- or down-regulated relative to Snail expression. We demonstrate that Snail binds to the Runx2 promoter and that repression of Runx2 transcription by Snail is dependent on specific E-box sequence within the promoter. With antisense morpholino oligonucleotide (MO)-mediated knockdown of Snail expression in zebrafish, we observed alterations in osteogenic potential. These results indicate that Snail plays a crucial role in osteogenic differentiation by acting as a direct Runx2 repressor.