Modeling by disruption and a selected-for partner for the nude locus.
Modeling by disruption and a selected-for partner for the nude locus.
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DOI：
10.15252/embr.201949804
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发表时间：
2021-03-03
期刊：
影响因子：
7.7
通讯作者：
Brissette JL
中科院分区：
文献类型：
--
作者：
Li J;Lee YK;Fu W;Whalen AM;Estable MC;Raftery LA;White K;Weiner L;Brissette JL
生物学中一个长期存在的问题是如何剖析没有易处理模型存在的性状。在这里，我们使用从未进化出毛发、胸腺或Foxn 1的动物来筛选像裸基因座（Foxn 1）这样的基因--哺乳动物毛发和胸腺发育的核心基因。果蝇在形态上被FOXN 1转录因子破坏，并通过果蝇基因功能的微弱减少而获救，揭示了与FOXN 1有效协同作用的分子，以实现戏剧性的，混乱的变化。在果蝇中的强协同作用/有效性预计反映了哺乳动物中的强选择/功能性（目的）;在外来环境（果蝇）中分子相互作用的破坏性越大，在其自然形成环境（哺乳动物）中就越有益。该方法将Aff 4鉴定为第一个裸样基因座，因为鼠AFF 4和FOXN 1协同诱导相似的皮肤/胸腺表型、相似的基因表达程序以及相同的转录步骤、预起始复合物形成。这些AFF 4功能是出乎意料的，因为AFF 4也在常见的转录延伸复合物中充当支架。最有可能的是，这种方法之所以有效，是因为互动的破坏力是其选择的必然结果-为了利益的力量。果蝇中与哺乳动物FOXN 1协同作用的基因的遗传筛选将Aff 4鉴定为裸样基因座。AFF 4与FOXN 1在哺乳动物毛发和胸腺发育中协同作用。
A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it will be in its natural, formative contexts (mammals). The approach identifies Aff4 as the first nude‐like locus, as murine AFF4 and FOXN1 cooperatively induce similar cutaneous/thymic phenotypes, similar gene expression programs, and the same step of transcription, pre‐initiation complex formation. These AFF4 functions are unexpected, as AFF4 also serves as a scaffold in common transcriptional‐elongation complexes. Most likely, the approach works because an interaction's power to disrupt is the inevitable consequence of its selected‐for power to benefit. A genetic screen in Drosophila for genes that synergize with mammalian FOXN1 identifies Aff4 as a nude‐like locus. AFF4 cooperates with FOXN1 in mammalian hair and thymus development.
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DOI：
10.1098/rspb.1979.0086
发表时间：
1979-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GOULD, SJ;LEWONTIN, RC
通讯作者：
LEWONTIN, RC
影响因子：
56.9
作者：
DENOOIJ, JC;HARIHARAN, IK
通讯作者：
HARIHARAN, IK
影响因子：
64.5
作者：
Freeman, M
通讯作者：
Freeman, M
影响因子：
11
作者：
Estable, MC;Naghavi, MH;Roeder, RG
通讯作者：
Roeder, RG
DOI：
10.1073/pnas.94.20.10750
发表时间：
1997-09-30
影响因子：
11.1
作者：
Gould, SJ
通讯作者：
Gould, SJ