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A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity Between HOXA11 and FOXO1
Citation: Erkenbrack, E. M., Ako-Asare, K., Miller, E., Tekelenburg, S., Thompson, J. R., & Romano, L. (2016). Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms. Development Genes and Evolution, 226(1), 37-45.
Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.

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Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms

Diverse sampling of organisms across the five ma- jor classes in the phylum Echinodermata is beginning to reveal much about the structure and function of gene regulatory net- works (GRNs) in development and evolution. Sea urchins are the most studied clade within this phylum, and recent work suggests there has been dramatic rewiring at the top of the skeletogenic GRN along the lineage leading to extant mem- bers of the euechinoid sea urchins. Such rewiring likely ac- counts for some of the observed developmental differences between the two major subclasses of sea urchins—cidaroids and euechinoids.
© 2016 Eric M Erkenbrack and Cell Press. All rights reserved.