Site pleiotropy of a stickleback Bmp6 enhancer.
Site pleiotropy of a stickleback Bmp6 enhancer.
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DOI：
10.1016/j.ydbio.2022.09.012
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发表时间：
2022-12
影响因子：
2.7
通讯作者：
Miller, Craig T.
中科院分区：
文献类型：
--
作者：
Rowley, Alyssa J.;Square, Tyler A.;Miller, Craig T.
发育和再生是由基因调控网络协调的，基因调控网络部分通过转录增强子来运作。尽管许多增强子是多效性的并且在多种组织中有活性，但是关于增强子多效性是否是由于1）位点多效性（其中在多种组织中的活性需要单个转录因子结合位点（TFBS））或2）调节不同组织中的表达的多个不同位点而引起的知之甚少。在这里，我们研究了棘鱼骨形态发生蛋白6（Bmp6）基因的内含子增强子的多效性。这种增强剂以前被证明可以调节牙齿数量和牙齿再生的进化变化，并且具有高度的多效性，在胚胎，幼虫和成年鱼的整个生命中，在鳍和牙齿中以及成鱼的心脏和肾脏中具有强大的活性。我们测试的假设，该增强子的多效性是由于网站多效性的进化保守的预测Foxc1 TFBS。转基因分析和定点诱变实验删除和扰乱这一预测的Foxc1 TFBS显示，结合位点是必需的增强子活性在整个胚胎，幼虫和成人发育的牙齿和鳍，并在成鱼的心脏和肾脏。总的来说，这些数据支持一个模型，其中该Bmp6增强子的多效性是由于位点多效性，并且该推定的结合位点是从胚胎到成人的多个解剖学位点中的增强子活性所需的。
Development and regeneration are orchestrated by gene regulatory networks that operate in part through transcriptional enhancers. Although many enhancers are pleiotropic and are active in multiple tissues, little is known about whether enhancer pleiotropy is due to 1) site pleiotropy, in which individual transcription factor binding sites (TFBS) are required for activity in multiple tissues, or 2) multiple distinct sites that regulate expression in different tissues. Here, we investigated the pleiotropy of an intronic enhancer of the stickleback Bone morphogenetic protein 6 (Bmp6) gene. This enhancer was previously shown to regulate evolved changes in tooth number and tooth regeneration, and is highly pleiotropic, with robust activity in both fins and teeth throughout embryonic, larval, and adult life, and in the heart and kidney in adult fish. We tested the hypothesis that the pleiotropy of this enhancer is due to site pleiotropy of an evolutionarily conserved predicted Foxc1 TFBS. Transgenic analysis and site-directed mutagenesis experiments both deleting and scrambling this predicted Foxc1 TFBS revealed that the binding site is required for enhancer activity in both teeth and fins throughout embryonic, larval, and adult development, and in the heart and kidney in adult fish. Collectively these data support a model where the pleiotropy of this Bmp6 enhancer is due to site pleiotropy and this putative binding site is required for enhancer activity in multiple anatomical sites from the embryo to the adult.
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影响因子：
11.8
作者：
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Kingsley, David M.
DOI：
10.1038/s41576-020-00311-x
发表时间：
2021-05
期刊：
Nature reviews. Genetics
影响因子：
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作者：
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通讯作者：
Wunderlich Z
DOI：
10.1073/pnas.1407567111
发表时间：
2014-09-23
影响因子：
11.1
作者：
Cleves, Phillip A.;Ellis, Nicholas A.;Miller, Craig T.
通讯作者：
Miller, Craig T.
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA