Hoxa2 selectively enhances Meis binding to change a branchial arch ground state.
Hoxa2 selectively enhances Meis binding to change a branchial arch ground state.
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DOI：
10.1016/j.devcel.2014.12.024
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发表时间：
2015-02-09
影响因子：
11.8
通讯作者：
Bobola, Nicoletta
中科院分区：
文献类型：
--
作者：
Amin, Shilu;Donaldson, Ian J.;Zannino, Denise A.;Hensman, James;Rattray, Magnus;Losa, Marta;Spitz, Francois;Ladam, Franck;Sagerstroem, Charles;Bobola, Nicoletta
Hox转录因子（TF）对于脊椎动物的发育至关重要，但这些进化保守蛋白在体内如何发挥作用仍不清楚。由于Hox蛋白具有众所周知的低结合特异性，因此据信它们与辅因子（主要是同源结构域TF Pbx和Meis）结合以选择它们的特异性靶标。我们映射绑定的Meis，Pbx，和Hoxa2在鳃弓，一系列的节段在发展中的脊椎动物头部。在Hox阳性和阴性拱中，Meis占有率基本相似。Hoxa2，它指定第二弓（IIBA）身份，承认一个子集的Meis预绑定网站，包含Hox基序。重要的是，在这些位点，Meis结合强烈增加。这种增强的Meis结合与活性增强子相一致，所述活性增强子与在IIBA中高度表达并由Hoxa2调节的基因相关联。这些发现表明，Hoxa2作为组织特异性辅因子，增强Meis与特定位点的结合，从而为IIBA提供其解剖学特性。Meis提供了所有鳃弓共有的基态Hoxa2识别第二弓中含有Hox基序的Meis预结合位点Hoxa2增强Meis结合，这与活性增强子一致，在这些位点Hoxa2调节Meis的基态结合以指示第二弓身份Hox转录因子指示鳃弓中的特定形态，脊椎动物头部发育中的一系列节段。Amin等人发现Hoxa2作为一种组织特异性辅因子，增强同源结构域转录因子Meis与特定位点的结合，这些位点为第二拱提供了其解剖学特征。
Hox transcription factors (TFs) are essential for vertebrate development, but how these evolutionary conserved proteins function in vivo remains unclear. Because Hox proteins have notoriously low binding specificity, they are believed to bind with cofactors, mainly homeodomain TFs Pbx and Meis, to select their specific targets. We mapped binding of Meis, Pbx, and Hoxa2 in the branchial arches, a series of segments in the developing vertebrate head. Meis occupancy is largely similar in Hox-positive and -negative arches. Hoxa2, which specifies second arch (IIBA) identity, recognizes a subset of Meis prebound sites that contain Hox motifs. Importantly, at these sites Meis binding is strongly increased. This enhanced Meis binding coincides with active enhancers, which are linked to genes highly expressed in the IIBA and regulated by Hoxa2. These findings show that Hoxa2 operates as a tissue-specific cofactor, enhancing Meis binding to specific sites that provide the IIBA with its anatomical identity. Meis provides a ground state that is common to all the branchial arches Hoxa2 recognizes Meis prebound sites in the second arch that contain Hox motifs Hoxa2 enhances Meis binding, which coincides with active enhancers, at these sites Hoxa2 modulates the ground-state binding of Meis to instruct second arch identity Hox transcription factors instruct specific morphologies in the branchial arches, a series of segments in the developing vertebrate head. Amin et al. found that Hoxa2 operates as a tissue-specific cofactor, enhancing binding of the homeodomain transcription factor Meis to specific sites that provide the second arch with its anatomical identity.
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影响因子：
3.7
作者：
Anderson M;Amin S;Luise F;Zeef L;Bobola N
通讯作者：
Bobola N
影响因子：
4.6
作者：
Deflorian, G;Tiso, N;Argenton, F
通讯作者：
Argenton, F
DOI：
10.1007/978-1-4939-1242-1_14
发表时间：
2014-01-01
期刊：
HOX GENES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Amin, Shilu;Bobola, Nicoletta
通讯作者：
Bobola, Nicoletta
影响因子：
64.8
作者：
HUNT, P;GULISANO, M;KRUMLAUF, R
通讯作者：
KRUMLAUF, R
影响因子：
11.4
作者：
DUBOULE, D;DOLLE, P
通讯作者：
DOLLE, P