The evolutionarily conserved leprecan gene: its regulation by Brachyury and its role in the developing Ciona notochord.
The evolutionarily conserved leprecan gene: its regulation by Brachyury and its role in the developing Ciona notochord.
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DOI：
10.1016/j.ydbio.2009.02.007
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发表时间：
2009-04-15
影响因子：
2.7
通讯作者：
Di Gregorio, Anna
中科院分区：
文献类型：
--
作者：
Dunn, Matthew P.;Di Gregorio, Anna
在肠道乔纳中，Leprecan被鉴定为脊索特异性转录因子Ciona brachyury(Ci-Bra)的靶标。通过筛选~14kb的Ci-leprecan基因座的顺式调节活性，我们已经确定了一个581bp的最小的脊索特异性顺式调节模块(CRM)，其活性依赖于位于ITS序列3‘端的T-box结合位点。这些位点在体外与GST-Ci-Bra融合蛋白特异性结合，而在体外取消结合的突变会导致体内调节活性的丧失或降低。对581个碱基的脊索CRM序列的连续删除表明，该序列也能够通过与Ci-Bra在脊索中利用的相同的T-box位点在肌肉细胞中直接表达，这些T-box位点在体外也被肌肉特异性T-box激活剂Ci-Tbx6b和Ci-Tbx6c结合。此外，我们还创建了旨在干扰Ci-leprecan功能的质粒，并对所产生的表型进行了分类，这些表型包括脊索细胞沿前后轴的可变错位。总之，这些观察结果提供了普遍适用于T-box转录因子及其目标序列的机制洞察力，以及关于Leprecan在早期脊索发育中功能的第一组线索。
In Ciona intestinalis, leprecan was identified as a target of the notochord-specific transcription factor Ciona Brachyury (Ci-Bra). By screening ~14 kb of the Ci-leprecan locus for cis-regulatory activity, we have identified a 581-bp minimal notochord-specific cis-regulatory module (CRM) whose activity depends upon T-box binding sites located at the 3’-end of its sequence. These sites are specifically bound in vitro by a GST-Ci-Bra fusion protein, and mutations that abolish binding in vitro result in loss or decrease of regulatory activity in vivo. Serial deletions of the 581-bp notochord CRM revealed that this sequence is also able to direct expression in muscle cells through the same T-box sites that are utilized by Ci-Bra in the notochord, which are also bound in vitro by the muscle-specific T-box activators Ci-Tbx6b and Ci-Tbx6c. Additionally, we created plasmids aimed to interfere with the function of Ci-leprecan and categorized the resulting phenotypes, which consist of variable dislocations of notochord cells along the anterior-posterior axis. Together, these observations provide mechanistic insights generally applicable to T-box transcription factors and their target sequences, as well as a first set of clues on the function of Leprecan in early chordate development.
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影响因子：
30.8
作者：
Cabral, Wayne A.;Chang, Weizhong;Marini, Joan C.
通讯作者：
Marini, Joan C.
影响因子：
2.7
作者：
Hotta, K;Takahashi, H;Satoh, N
通讯作者：
Satoh, N
影响因子：
4.6
作者：
Imai, KS;Hino, K;Satou, Y
通讯作者：
Satou, Y
DOI：
10.1007/bf00343819
发表时间：
1969-01-01
期刊：
ZEITSCHRIFT FUR ZELLFORSCHUNG UND MIKROSKOPISCHE ANATOMIE
影响因子：
--
作者：
CLONEY, RA
通讯作者：
CLONEY, RA
影响因子：
2.4
作者：
Grotmol, Sindre;Kryvi, Harald;Totland, Geir K.
通讯作者：
Totland, Geir K.