Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.
Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.
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DOI：
10.1038/s41598-018-21194-3
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发表时间：
2018-02-16
影响因子：
4.6
通讯作者：
Hiraki Y
中科院分区：
文献类型：
--
作者：
Shukunami C;Takimoto A;Nishizaki Y;Yoshimoto Y;Tanaka S;Miura S;Watanabe H;Sakuma T;Yamamoto T;Kondoh G;Hiraki Y
腱调节蛋白 (Tnmd) 是一种 II 型跨膜糖蛋白，主要在肌腱和韧带中表达。我们发现 scleraxis (Scx) 是碱性螺旋-环-螺旋转录因子 Twist 家族的成员，是肌腱细胞中 Tnmd 表达的转录激活剂。在胚胎发育过程中，Scx 的表达先于 Tnmd 的表达。由转录激活因子样效应核酸酶介导的基因破坏产生的 Scx 缺陷小鼠的肌腱和韧带中几乎不存在 Tnmd 表达。在大鼠肌腱细胞的连续传代过程中，Tnmd mRNA 水平显着降低。小干扰 RNA 沉默 Scx 显着抑制肌腱细胞中内源性 Tnmd mRNA 水平。小鼠 Tnmd 在约 1 kb 5' 侧翼区域包含 5 个 E-box 位点。含有 TATA 盒的 174 个碱基对基因组片段驱动肌腱细胞中的转录。肌腱细胞中 Tnmd 上游区域（-1030 至 -295）的增强子活性增加，但 NIH3T3 和 C3H10T1/2 细胞中则没有。 Scx 和 Twist1 作为与 E12 或 E47 的异二聚体优先结合到 CAGATG 或 CATCTG 以及 5'-侧翼区域的反式激活，分别通过电泳迁移率变动和双荧光素酶测定证实。 Scx 通过这些 E-box 直接反式激活 Tnmd，以正向调节肌腱细胞的分化和成熟。
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.
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影响因子：
12.3
作者：
Jones S
通讯作者：
Jones S
影响因子：
4.6
作者：
Sakuma, Tetsushi;Ochiai, Hiroshi;Kaneko, Takehito;Mashimo, Tomoji;Tokumasu, Daisuke;Sakane, Yuto;Suzuki, Ken-ichi;Miyamoto, Tatsuo;Sakamoto, Naoaki;Matsuura, Shinya;Yamamoto, Takashi
通讯作者：
Yamamoto, Takashi
影响因子：
4.8
作者：
Lejard, Veronique;Brideau, Gaelle;Rossert, Jerome
通讯作者：
Rossert, Jerome
DOI：
10.1016/j.biocel.2009.10.003
发表时间：
2010-01-01
影响因子：
4
作者：
Furumatsu, Takayuki;Shukunami, Chisa;Ozaki, Toshifumi
通讯作者：
Ozaki, Toshifumi
影响因子：
4.6
作者：
Murchison, Nicholas D.;Price, Brian A.;Schweitzer, Ronen
通讯作者：
Schweitzer, Ronen