Wnt3a signal pathways activate MyoD expression by targeting cis-elements inside and outside its distal enhancer

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题名:	Wnt3a signal pathways activate MyoD expression by targeting cis-elements inside and outside its distal enhancer
作者:	陳盛良;Pan, Yu Chih;Wang, Xiao Wen;Teng, Han Feng;Wu, Yi Ju;Chang, Hsuan Chia;Chen, Shen Liang
贡献者:	生醫理工學院生命科學系
关键词:	Cell Line;Gene Expression Regulation - physiology;Humans;MyoD Protein - biosynthesis;MyoD Protein - genetics;Myogenic Regulatory Factor 5 - genetics;Myogenic Regulatory Factor 5 - metabolism;Original Paper;Paired Box Transcription Factors - genetics;Paired Box Transcription Factors - metabolism;PAX3 Transcription Factor;PAX7 Transcription Factor - genetics;PAX7 Transcription Factor - metabolism;Response Elements - physiology;Wnt Signaling Pathway - physiology;Wnt3A Protein - genetics;Wnt3A Protein - metabolism
日期:	2015-02-05
上传时间:	2026-04-23 11:14:23 (UTC+8)
出版者:	Portland Press, Ltd.;England: Portland Press Ltd
摘要:	摘要： Wnt proteins are secreted cytokines and several Wnts are expressed in the developing somites and surrounding tissues. Without proper Wnt stimulation, the organization of the dermomyotome and myotome can become defective. These Wnt signals received by somitic cells can lead to activation of Pax3/Pax7 and myogenic regulatory factors (MRFs), especially Myf5 and MyoD. However, it is currently unknown whether Wnts activate Myf5 and MyoD through direct targeting of their cis-regulatory elements or via indirect pathways. To clarify this issue, in the present study, we tested the regulation of MyoD cis-regulatory elements by Wnt3a secreted from human embryonic kidney (HEK)-293T cells. We found that Wnt3a activated the MyoD proximal 6.0k promoter (P6P) only marginally, but highly enhanced the activity of the composite P6P plus distal enhancer (DE) reporter through canonical and non-canonical pathways. Further screening of the intervening fragments between the DE and the P6P identified a strong Wnt-response element (WRE) in the upstream −8 to −9k region (L fragment) that acted independently of the DE, but was dependent on the P6P. Deletion of a Pax3/Pax7-targeted site in the L fragment significantly reduced its response to Wnt3a, implying that Wnt3a activates the L fragment partially through Pax3/Pax7 action. Binding of β-catenin and Pax7 to their target sites in the DE and the L fragment respectively was also demonstrated by ChIP. These observations demonstrated the first time that Wnt3a can directly activate MyoD expression through targeting cis-elements in the DE and the L fragment. 其他題名： Biosci Rep 出版者： England: Portland Press Ltd 出版日期： 2015-03-18 出處： Bioscience Reports, 2015-03, Vol.35 (2), p.e00180- 資源來源： Agricultural & Environmental Science Collection 版權： 2015 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. 2015 識別號： ISSN: 0144-8463 識別號： ISSN: 1573-4935 識別號： EISSN: 1573-4935 識別號： DOI: 10.1042/bsr20140177 識別號： PMID: 25651906
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