Modeling by disruption and a selected‐for partner for the nude locus

Autor: Anne M Whalen, Jian Li, Wenyu Fu, Lorin Weiner, Mario Clemente Estable, Laurel A. Raftery, Yun-Kyoung Lee, Janice L. Brissette, Kristin White
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBO Reports
EMBO Rep
ISSN: 1469-3178
1469-221X
Popis: 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.
Databáze: OpenAIRE
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