Transcriptional rewiring of the sex determining dmrt1 gene duplicate by transposable elements.
Transcriptional rewiring of the sex determining dmrt1 gene duplicate by transposable elements.
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DOI：
10.1371/journal.pgen.1000844
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发表时间：
2010-02-12
期刊：
影响因子：
4.5
通讯作者：
Schartl M
中科院分区：
文献类型：
--
作者：
Herpin A;Braasch I;Kraeussling M;Schmidt C;Thoma EC;Nakamura S;Tanaka M;Schartl M
真核生物基因表达的调控和协调依赖于转录和转录后调控网络。进化的创新和适应往往需要这种网络的快速变化。长期以来，人们一直假设转座因子（TE）可能有助于调节相互作用的重新布线。最近出现的是，TE可能会引入现成的转录因子结合位点，以改变捕获它们的启动子。性别决定是基因调控结构具有显著可塑性的过程。虽然性别决定级联的下游成分在进化上是保守的，但主调节因子可以在生物群体之间切换，甚至在物种间或种群之间切换。在青鳉鱼（Oryzias latipes）中，Y染色体上的dmrt 1的重复拷贝（称为dmrt 1bY或DMY）被证明是雄性发育的主要调节因子，类似于哺乳动物中的Sry。我们发现，dmrt 1bY基因已获得了一个新的反馈下调其表达。此外，常染色体dmrt 1a基因还能够通过结合嵌套在dmrt 1bY近端启动子区域内的独特靶Dmrt 1位点来调节其复制的paramount的转录。我们可以追溯到一个高度保守的序列内的一种新型的TE插入dmrt 1bY的上游区域后不久的重复事件，这种新的调控元件。我们的数据提供了功能的证据TE的作用，在转录网络重新布线子和/或新功能的重复基因。在dmrt 1bY的特殊情况下，这有助于创建新的性别决定基因层次。进化的创新和适应往往需要基因调控的快速变化。转座因子是真核生物基因组中最具活力的部分。转座因子的插入可以通过提供新的调控元件来影响周围基因的表达。一个长期存在的假说认为，转座因子的扩散可能会重新连接基因之间的调控联系，从而改变调控网络和洗牌的调控级联。性别决定级联是一个具有显著可塑性的调节层次。在动物进化的过程中，新的主调节因子经常取代性别决定基因。在青鳉鱼中，dmrt 1转录因子基因dmrt 1bY的复制品已成为性别主调节器。相反，它的祖先dmrt 1a在性别决定级联反应中处于下游位置。我们表明，在dmrt 1基因复制后，通过将转座因子插入性染色体上dmrt 1bY基因的调节区，建立了新的层次结构。这个转座因子，窝藏Dmrt 1结合位点，使自我和交叉调节Dmrt 1蛋白的dmrt 1bY表达。因此，我们的研究为转座因子在基因调控网络的重新布线中的重要作用提供了强有力的证据。
Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE) might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish (Oryzias latipes) a duplicated copy of dmrt1, designated dmrt1bY or DMY, on the Y chromosome was shown to be the master regulator of male development, similar to Sry in mammals. We found that the dmrt1bY gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal dmrt1a gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the dmrt1bY proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of dmrt1bY shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of dmrt1bY, this contributed to create new hierarchies of sex-determining genes. Evolutionary innovations and adaptations often require rapid changes in gene regulation. Transposable elements constitute the most dynamic part of eukaryotic genomes. Insertions of transposable elements can influence the expression of surrounding genes by donating new regulatory elements. A longstanding hypothesis postulates that the dispersal of transposable elements may rewire regulatory links between genes, thereby changing regulatory networks and shuffling regulatory cascades. A regulatory hierarchy of remarkable plasticity is the sex determination cascade. In the course of animal evolution, new master regulators frequently replace the sex determination gene on top of the hierarchy. In the medaka fish, a duplicate of the dmrt1 transcription factor gene, dmrt1bY, has become the sex master regulator. Its ancestor dmrt1a, in contrast, has a downstream position in the sex determination cascade. We show that after the duplication of the dmrt1 gene, the new hierarchy has been established by the insertion of a transposable element into the regulatory region of the dmrt1bY gene on the sex chromosome. This transposable element, harboring a Dmrt1 binding site, enables the self- and cross-regulation of dmrt1bY expression by Dmrt1 proteins. Our study therefore provides strong evidence for the important role of transposable elements in the rewiring of gene regulatory networks.
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影响因子：
9.2
作者：
Kondo, M;Nanda, I;Schartl, M
通讯作者：
Schartl, M
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1002/jez.b.21053
发表时间：
2005-09-15
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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作者：
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