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タイトル: Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes
著者: Shukunami, Chisa
Takimoto, Aki
Nishizaki, Yuriko
Yoshimoto, Yuki
Tanaka, Seima
Miura, Shigenori
Watanabe, Hitomi  kyouindb  KAKEN_id
Sakuma, Tetsushi
Yamamoto, Takashi
Kondoh, Gen
Hiraki, Yuji
著者名の別形: 宿南, 知佐
滝本, 晶
西崎, 有利子
三浦, 重徳
渡邊, 仁美
近藤, 玄
開, 祐司
発行日: 16-Feb-2018
出版者: Springer Nature
誌名: Scientific Reports
巻: 8
論文番号: 3155
抄録: Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5′-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (−1030 to −295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5′-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.
著作権等: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/234567
DOI(出版社版): 10.1038/s41598-018-21194-3
PubMed ID: 29453333
出現コレクション:学術雑誌掲載論文等

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