Fine tuning of craniofacial morphology by distant-acting enhancers.
Fine tuning of craniofacial morphology by distant-acting enhancers.
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DOI：
10.1126/science.1241006
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发表时间：
2013-10-25
期刊：
影响因子：
--
通讯作者：
Visel A
中科院分区：
文献类型：
--
作者：
Attanasio C;Nord AS;Zhu Y;Blow MJ;Li Z;Liberton DK;Morrison H;Plajzer-Frick I;Holt A;Hosseini R;Phouanenavong S;Akiyama JA;Shoukry M;Afzal V;Rubin EM;FitzPatrick DR;Ren B;Hallgrímsson B;Pennacchio LA;Visel A
人类面部和头骨的形状在很大程度上是由基因决定的，但颅面形态的遗传驱动因素仍然知之甚少。本研究采用表观基因组分析、转基因小鼠候选增强子序列的体内表征和靶向缺失实验相结合的方法来研究远端作用增强子在颅面发育中的作用。我们发现了复杂的调控景观，包括驱动发育表达模式显著的空间复杂性的增强子。从小鼠基因组中删除单个颅面增强子导致颅面形状的显着改变，证明了它们在定义面部和头骨形态方面的功能重要性。这些结果表明，增强子在哺乳动物颅面发育中起着普遍的作用，并表明增强子序列的变化有助于人类面部形态的形成。
The shape of the human face and skull is largely genetically determined, but the genetic drivers of craniofacial morphology remain poorly understood. Here we used a combination of epigenomic profiling, in vivo characterization of candidate enhancer sequences in transgenic mice, and targeted deletion experiments to examine the role of distant-acting enhancers in craniofacial development. We identified complex regulatory landscapes, consisting of enhancers that drive a remarkable spatial complexity of developmental expression patterns. Deletion of individual craniofacial enhancers from the mouse genome resulted in significant alterations of craniofacial shape, demonstrating their functional importance in defining face and skull morphology. These results demonstrate that enhancers play a pervasive role in mammalian craniofacial development and suggest that enhancer sequence variation contributes to human facial morphology.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
2.6
作者：
MacKenzie, A;Purdie, L;Hill, RE
通讯作者：
Hill, RE
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
2
作者：
Mangold, Elisabeth;Reutter, Heiko;Lacava, Amalia Diaz
通讯作者：
Lacava, Amalia Diaz