Modular evolution of DNA-binding preference of a Tbrain transcription factor provides a mechanism for modifying gene regulatory networks.
Modular evolution of DNA-binding preference of a Tbrain transcription factor provides a mechanism for modifying gene regulatory networks.
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DOI：
10.1093/molbev/msu213
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发表时间：
2014-10
影响因子：
10.7
通讯作者：
Hinman VF
中科院分区：
文献类型：
--
作者：
Cheatle Jarvela AM;Brubaker L;Vedenko A;Gupta A;Armitage BA;Bulyk ML;Hinman VF
基因调控网络(GRN)描述了将单细胞受精卵带入多细胞生物体的转录状态的进展。已有文献证明，GRN可以通过突变而广泛进化为顺式调节模块(CRM)。结合这些CRM的转录因子蛋白也可能进化以产生新奇的东西。然而，编码变化被认为是比较罕见的，因为转录因子是多功能的，因此更多地受到限制，以不会产生广泛有害影响的方式进化。最近的技术进步发现了DNA结合能力的惊人变化，以至于单个转录因子可以识别首选的初级基序和额外的次级基序。这在功能上提供了模块化的来源。在这里，我们证明了同源转录因子也可以进化出对二级结合基序的改变的偏好，从而为GRN的进化提供了一种未知的机制。利用蛋白质结合芯片、表面等离子共振和活体报告基因分析，我们发现两种棘皮动物海星(Patiria Mini Ata)和海胆(Strongyloctrotus Puratus)的TBrain蛋白同源基因在DNA结合偏好上存在重要差异。虽然两个同源基因识别相同的一级基序，但只有海星TBR也有二级结合基序。我们的体内分析表明，这种差异可能允许在调控时间上发生更大的进化变化。这揭示了一层转录因子结合的分歧，这可能存在于许多对同源基因中。我们假设这种分歧提供了模块化，允许同源转录因子通过修改与二级位点的结合而在GRN中进化出新的角色。
Gene regulatory networks (GRNs) describe the progression of transcriptional states that take a single-celled zygote to a multicellular organism. It is well documented that GRNs can evolve extensively through mutations to cis-regulatory modules (CRMs). Transcription factor proteins that bind these CRMs may also evolve to produce novelty. Coding changes are considered to be rarer, however, because transcription factors are multifunctional and hence are more constrained to evolve in ways that will not produce widespread detrimental effects. Recent technological advances have unearthed a surprising variation in DNA-binding abilities, such that individual transcription factors may recognize both a preferred primary motif and an additional secondary motif. This provides a source of modularity in function. Here, we demonstrate that orthologous transcription factors can also evolve a changed preference for a secondary binding motif, thereby offering an unexplored mechanism for GRN evolution. Using protein-binding microarray, surface plasmon resonance, and in vivo reporter assays, we demonstrate an important difference in DNA-binding preference between Tbrain protein orthologs in two species of echinoderms, the sea star, Patiria miniata, and the sea urchin, Strongylocentrotus purpuratus. Although both orthologs recognize the same primary motif, only the sea star Tbr also has a secondary binding motif. Our in vivo assays demonstrate that this difference may allow for greater evolutionary change in timing of regulatory control. This uncovers a layer of transcription factor binding divergence that could exist for many pairs of orthologs. We hypothesize that this divergence provides modularity that allows orthologous transcription factors to evolve novel roles in GRNs through modification of binding to secondary sites.
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DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
14.8
作者：
Berger, Michael F.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
影响因子：
14.9
作者：
Cameron RA;Samanta M;Yuan A;He D;Davidson E
通讯作者：
Davidson E
DOI：
10.1073/pnas.2235868100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hinman, VF;Nguyen, AT;Davidson, EH
通讯作者：
Davidson, EH
影响因子：
46.9
作者：
Berger, Michael F.;Philippakis, Anthony A.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.