Improved genome assembly of American alligator genome reveals conserved architecture of estrogen signaling.
Improved genome assembly of American alligator genome reveals conserved architecture of estrogen signaling.
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DOI：
10.1101/gr.213595.116
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发表时间：
2017-05
期刊：
影响因子：
7
通讯作者：
Green RE
中科院分区：
文献类型：
--
作者：
Rice ES;Kohno S;John JS;Pham S;Howard J;Lareau LF;O'Connell BL;Hickey G;Armstrong J;Deran A;Fiddes I;Platt RN 2nd;Gresham C;McCarthy F;Kern C;Haan D;Phan T;Schmidt C;Sanford JR;Ray DA;Paten B;Guillette LJ Jr;Green RE
美洲短吻鳄（Alligator mississippiensis）和所有鳄鱼一样，具有温度依赖性的性别决定，胚胎的性别由卵在发育的关键时期的孵化温度决定。雄性和雌性短吻鳄之间缺乏遗传差异，这就留下了一个问题，即负责性别决定和分化的基因是如何调节的。对这个问题的理解来自于这样一个事实，即将胚胎在产生雄性的温度下孵育，雌激素会导致它发育卵巢。由于雌激素反应元件已知可以长距离调节基因，因此连续的基因组组装对于预测和理解它们的影响至关重要。我们提出了一个改进的美国短吻鳄基因组组装，支架与体外邻近连接（芝加哥）的数据。我们使用这种组装支架其他两个鳄鱼基因组的基础上同线性。我们对美洲鳄胚胎的组织进行RNA测序，以寻找在雄性与雌性生产温度下孵育的胚胎之间差异表达的基因。最后，我们使用改进的连续性，我们的组装沿着与当前模型的CTCF介导的染色质循环，以预测可能包含雌激素反应基因的基因组区域。我们发现，这些地区是显着丰富的基因与女性偏见的表达后，在发育中的性腺的关键时期，在此期间，性别是由孵化温度。因此，我们得出结论，雌激素信号是一个主要的驱动程序，女性偏向的基因表达在后温度敏感期性腺。
The American alligator, Alligator mississippiensis, like all crocodilians, has temperature-dependent sex determination, in which the sex of an embryo is determined by the incubation temperature of the egg during a critical period of development. The lack of genetic differences between male and female alligators leaves open the question of how the genes responsible for sex determination and differentiation are regulated. Insight into this question comes from the fact that exposing an embryo incubated at male-producing temperature to estrogen causes it to develop ovaries. Because estrogen response elements are known to regulate genes over long distances, a contiguous genome assembly is crucial for predicting and understanding their impact. We present an improved assembly of the American alligator genome, scaffolded with in vitro proximity ligation (Chicago) data. We use this assembly to scaffold two other crocodilian genomes based on synteny. We perform RNA sequencing of tissues from American alligator embryos to find genes that are differentially expressed between embryos incubated at male- versus female-producing temperature. Finally, we use the improved contiguity of our assembly along with the current model of CTCF-mediated chromatin looping to predict regions of the genome likely to contain estrogen-responsive genes. We find that these regions are significantly enriched for genes with female-biased expression in developing gonads after the critical period during which sex is determined by incubation temperature. We thus conclude that estrogen signaling is a major driver of female-biased gene expression in the post-temperature sensitive period gonads.