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JCS ePress online publication date 20 Mar 2007
doi: 10.1242/jcs.000067

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Research Article

Comparative roles of Twist-1 and Id1 in transcriptional regulation by BMP signaling


Masanori Hayashi, Keisuke Nimura, Katsunobu Kashiwagi, Taku Harada, Kunio Takaoka, Hiroyuki Kato, Katsuto Tamai, and Yasufumi Kaneda*
* Author for correspondence (e-mail: kaneday{at}gts.med.osaka-u.ac.jp)

Basic helix-loop-helix (bHLH) transcription factors are known as key regulators for mesenchymal differentiation. The present study showed that overexpression of Twist-1, a bHLH transcription factor, suppresses bone morphogenetic protein (BMP)-induced osteoblast differentiation, and downregulation of endogenous Twist-1 enhances BMP signaling. Maximal inhibition of BMP signaling was observed when Twist-1 was bound to E47, which markedly enhanced the stability of Twist-1. Co-immunoprecipitation assays revealed that Twist-1 formed a complex with Smad4 and histone deacetylase (HDAC) 1 in MC3T3-E1 cells stably expressing Twist-1. With trichostatin, an HDAC inhibitor, osteogenic factors such as alkaline phosphatase, Runx2 and osteopontin increased. Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4.
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