Aug 19, 2014 - REGULAR ARTICLE. Double homeobox gene, Duxbl, promotes myoblast proliferation and abolishes myoblast differentiation by blocking MyoD.
Double homeobox gene, Duxbl, promotes myoblast proliferation and abolishes myoblast differentiation by blocking MyoD transactivation Shey-Lin Wu, Guo-Zili Li, Chin-Yi Chou, Ming-Shiun Tsai, Yi-Pei Chen, Chung-Jung Li, Gan-Guang Liou, WenWei Chang, Shen-Liang Chen, et al. Cell and Tissue Research ISSN 0302-766X Volume 358 Number 2 Cell Tissue Res (2014) 358:551-566 DOI 10.1007/s00441-014-1974-x
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Author's personal copy Cell Tissue Res (2014) 358:551–566 DOI 10.1007/s00441-014-1974-x
REGULAR ARTICLE
Double homeobox gene, Duxbl, promotes myoblast proliferation and abolishes myoblast differentiation by blocking MyoD transactivation Shey-Lin Wu & Guo-Zili Li & Chin-Yi Chou & Ming-Shiun Tsai & Yi-Pei Chen & Chung-Jung Li & Gan-Guang Liou & Wen-Wei Chang & Shen-Liang Chen & Sue-Hong Wang
Received: 11 February 2014 / Accepted: 21 July 2014 / Published online: 19 August 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Homeobox genes encode transcription factors that regulate embryonic development programs including organogenesis, axis formation and limb development. Previously, we identified and cloned a mouse double homeobox gene, Duxbl, whose homeodomain exhibits the highest identity (67 %) to human DUX4, a candidate gene of facioscapulohumeral muscular dystrophy (FSHD). Duxbl proteins have been shown to be expressed in elongated myocytes and myotubes of trunk and limb muscles during embryogenesis. In this study, we found that Duxbl maintained low expression levels in various adult muscles. Duxbl proteins were induced to express in activated satellite cells and colocalized with MyoG, a myogenic differentiating marker. Furthermore, Duxbl proteins were not detected in quiescent satellite cells but detected in
regenerated myocytes and colocalized with MyoD and MyoG following cardiotoxin-induced muscle injury. Ectopic Duxbl overexpressions in C2C12 myoblast cells promoted cell proliferation through mainly enhancing cyclin D1 and hyperphosphorylated retinoblastoma protein but reducing p21 expression. However, Duxbl overexpression in C2C12 cells inhibited myogenic differentiation by decreasing MyoD downstream gene expressions, including M-cadherin, MyoG, p21 and cyclin D3 but not MyoD itself. Duxbl overexpressions also promoted cell proliferation but blocked MyoD-induced myogenic conversion in multipotent mesenchymal C3H10T1/ 2 cells. In addition, results of a luciferase reporter assay suggest that Duxbl negatively regulated MyoG promoter activity through the proximal two E boxes. In conclusion, these
Shey-Lin Wu, Guo-Zili Li and Chin-Yi Chou contributed equally in this work This work was supported by grants from the National Science Council of Taiwan (NSC97-2320-B-040-010-MY3, NSC100-2320-B-040-012), Chung Shan Medical University (CSMU-INT-101-18) and Chang-Hua Christian Hospital (102-CCH-IRP-036). Electronic supplementary material The online version of this article (doi:10.1007/s00441-014-1974-x) contains supplementary material, which is available to authorized users. G.
