The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression.
Osteoblasts 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.
Park
Su Jin
SJ
Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, Republic of Korea.
Jung
Seung-Hyun
SH
Jogeswar
Gadi
G
Ryoo
Hyun-Mo
HM
Yook
Jong In
JI
Choi
Han Seok
HS
Rhee
Yumie
Y
Kim
Cheol-Hee
CH
Lim
Sung-Kil
SK
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors