Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly.
Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly.
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DOI：
10.1016/j.devcel.2011.12.010
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发表时间：
2012-02-14
影响因子：
11.8
通讯作者：
Hill, Robert E.
中科院分区：
文献类型：
--
作者：
Lettice, Laura A.;Williamson, Iain;Wiltshire, John H.;Peluso, Silvia;Devenney, Paul S.;Hill, Alison E.;Essafi, Abdelkader;Hagman, James;Mort, Richard;Grimes, Graeme;DeAngelis, Carlo L.;Hill, Robert E.
Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of polarizing activity (ZPA), and this expression is controlled from a long distance by the cis-regulator ZRS. Here, members of two groups of ETS transcription factors are shown to act directly at the ZRS mediating a differential effect on Shh, defining its spatial expression pattern. Occupancy at multiple GABPα/ETS1 sites regulates the position of the ZPA boundary, whereas ETV4/ETV5 binding restricts expression outside the ZPA. The ETS gene family is therefore attributed with specifying the boundaries of the classical ZPA. Two point mutations within the ZRS change the profile of ETS binding and activate Shh expression at an ectopic site in the limb bud. These molecular changes define a pathogenetic mechanism that leads to preaxial polydactyly (PPD). ► ETS factors bind to the Shh enhancer, ZRS, to specify spatial expression in the limb ► ETS1 and GABPα bind to multiple sites to define the expression domain boundary ► ETV4 and ETV5 bind to inhibit expression outside that spatial domain ► Mutations that change the ETS binding profile cause limb abnormalities A long-range limb-specific enhancer controls Sonic hedgehog expression in a spatiotemporally restricted manner. Lettice et al. identify ETS-binding sites within this enhancer that mediate antagonistic interactions between different ETS transcription factor clades. Mutations in the enhancer that change the balance of power between ETS factors cause limb abnormalities.
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影响因子：
7
作者：
Lifanov, AP;Makeev, VJ;Papatsenko, DA
通讯作者：
Papatsenko, DA
DOI：
10.1073/pnas.112212199
发表时间：
2002-05-28
影响因子：
11.1
作者：
Lettice, LA;Horikoshi, T;Noji, S
通讯作者：
Noji, S
影响因子：
2.6
作者：
Ristevski, S;Tam, PPL;Kola, I
通讯作者：
Kola, I
DOI：
10.1198/016214506000001211
发表时间：
2007-03-01
影响因子：
3.7
作者：
Efron, Bradley
通讯作者：
Efron, Bradley
影响因子：
10.5
作者：
Hollenhorst, Peter C.;Shah, Atul A.;Graves, Barbara J.
通讯作者：
Graves, Barbara J.