title: The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression.
abstract: 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.
authors.affiliation: Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Gadi
authors.initials: G
authors.lastname: Jogeswar
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Jong In
authors.initials: JI
authors.lastname: Yook
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Yumie
authors.initials: Y
authors.lastname: Rhee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Sung-Kil
authors.initials: SK
authors.lastname: Lim
mesh_terms: 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*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors