Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25

Yukio Nakamura; Koji Yamamoto; Xinjun He; Bungo Otsuki; Youngwoo Kim; Hiroki Murao; Tsunemitsu Soeda; Noriyuki Tsumaki; Jian Min Deng; Zhaoping Zhang; Richard R. Behringer; Benoit De Crombrugghe; John H. Postlethwait; Matthew L. Warman; Takashi Nakamura; Haruhiko Akiyama

doi:10.1038/ncomms1242

Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25

Yukio Nakamura, Koji Yamamoto, Xinjun He, Bungo Otsuki, Youngwoo Kim, Hiroki Murao, Tsunemitsu Soeda, Noriyuki Tsumaki, Jian Min Deng, Zhaoping Zhang, Richard R. Behringer, Benoit De Crombrugghe, John H. Postlethwait, Matthew L. Warman, Takashi Nakamura, Haruhiko Akiyama

Genetics

Research output: Contribution to journal › Article › peer-review

123 Scopus citations

Abstract

Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.

Original language	English (US)
Article number	251
Journal	Nature communications
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/ncomms1242
State	Published - 2011

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Nakamura, Y., Yamamoto, K., He, X., Otsuki, B., Kim, Y., Murao, H., Soeda, T., Tsumaki, N., Deng, J. M., Zhang, Z., Behringer, R. R., De Crombrugghe, B., Postlethwait, J. H., Warman, M. L., Nakamura, T., & Akiyama, H. (2011). Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25. Nature communications, 2(1), Article 251. https://doi.org/10.1038/ncomms1242

Nakamura, Y, Yamamoto, K, He, X, Otsuki, B, Kim, Y, Murao, H, Soeda, T, Tsumaki, N, Deng, JM, Zhang, Z, Behringer, RR, De Crombrugghe, B, Postlethwait, JH, Warman, ML, Nakamura, T & Akiyama, H 2011, 'Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25', Nature communications, vol. 2, no. 1, 251. https://doi.org/10.1038/ncomms1242

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abstract = "Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.",

author = "Yukio Nakamura and Koji Yamamoto and Xinjun He and Bungo Otsuki and Youngwoo Kim and Hiroki Murao and Tsunemitsu Soeda and Noriyuki Tsumaki and Deng, {Jian Min} and Zhaoping Zhang and Behringer, {Richard R.} and {De Crombrugghe}, Benoit and Postlethwait, {John H.} and Warman, {Matthew L.} and Takashi Nakamura and Haruhiko Akiyama",

note = "Funding Information: We thank Andreas Schedl, Stephen O{\textquoteright}Gorman and James F. Martin for valuable help. These studies were supported by a Grant-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (#20659231), a Takeda Science Foundation grant to H.A., a National Institutes of Health HD30284 grant to R.R.B. and National Institutes of Health grants HD022486 and DE020076 to J.H.P.",

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AU - Kim, Youngwoo

AU - Murao, Hiroki

AU - Soeda, Tsunemitsu

AU - Tsumaki, Noriyuki

AU - Deng, Jian Min

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AU - Warman, Matthew L.

AU - Nakamura, Takashi

AU - Akiyama, Haruhiko

N1 - Funding Information: We thank Andreas Schedl, Stephen O’Gorman and James F. Martin for valuable help. These studies were supported by a Grant-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (#20659231), a Takeda Science Foundation grant to H.A., a National Institutes of Health HD30284 grant to R.R.B. and National Institutes of Health grants HD022486 and DE020076 to J.H.P.

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N2 - Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.

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Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25

Abstract

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