Genetic evidence for conserved non-coding element function across species-the ears have it.
Genetic evidence for conserved non-coding element function across species-the ears have it.
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DOI：
10.3389/fphys.2014.00007
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发表时间：
2014
影响因子：
4
通讯作者：
Cox TC
中科院分区：
文献类型：
--
作者：
Turner EE;Cox TC
比较不同脊椎动物物种的基因组序列，发现许多高度保守的区域似乎不编码蛋白质或功能性RNA。通常，这些“保守的非编码元件”或CNE可以在转基因模型中将基因表达引导到特定组织，证明它们具有调节功能。CNE经常在“发育”基因，特别是转录因子附近发现，这意味着这些元件在发育中具有重要的调节作用。然而，证明CNE跨物种调节功能的实际例子很少，最近对小鼠中几种CNE的功能丧失研究显示出相对较小的影响。在这篇观点文章中，我们讨论了在“花式”大鼠和高地牛中的新发现，证明Hmx1基因附近的CNE功能对正常外耳发育至关重要，并且当被破坏时可以模拟小鼠和人类中Hmx1编码突变的功能丧失。这些发现为CNEs在不同物种中的保守发育作用提供了重要支持，并加强了CNEs应在基因组规模测序时代持续寻找人类发育障碍遗传原因的过程中进行系统研究的概念。
Comparison of genomic sequences from diverse vertebrate species has revealed numerous highly conserved regions that do not appear to encode proteins or functional RNAs. Often these “conserved non-coding elements,” or CNEs, can direct gene expression to specific tissues in transgenic models, demonstrating they have regulatory function. CNEs are frequently found near “developmental” genes, particularly transcription factors, implying that these elements have essential regulatory roles in development. However, actual examples demonstrating CNE regulatory functions across species have been few, and recent loss-of-function studies of several CNEs in mice have shown relatively minor effects. In this Perspectives article, we discuss new findings in “fancy” rats and Highland cattle demonstrating that function of a CNE near the Hmx1 gene is crucial for normal external ear development and when disrupted can mimic loss-of function Hmx1 coding mutations in mice and humans. These findings provide important support for conserved developmental roles of CNEs in divergent species, and reinforce the concept that CNEs should be examined systematically in the ongoing search for genetic causes of human developmental disorders in the era of genome-scale sequencing.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
7
作者：
Simões-Costa M;Bronner ME
通讯作者：
Bronner ME
影响因子：
2.7
作者：
Howard, ML;Davidson, EH
通讯作者：
Davidson, EH
影响因子：
4.4
作者：
Sandelin A;Bailey P;Bruce S;Engström PG;Klos JM;Wasserman WW;Ericson J;Lenhard B
通讯作者：
Lenhard B
影响因子：
9.2
作者：
Sharpe, J;Lettice, L;Krumlauf, R
通讯作者：
Krumlauf, R