The binding of some transcription factors has been shown to diverge substantially between closely related species. Here we show that the binding of the developmental transcription factor Twist is highly conserved across six Drosophila species, revealing strong functional constraints at its enhancers. Conserved binding correlates with sequence motifs for Twist and its partners, permitting the de novo discovery of their combinatorial binding. It also includes over 10,000 low-occupancy sites near the detection limit, which tend to mark enhancers of later developmental stages. These results suggest that developmental enhancers can be highly evolutionarily constrained, presumably because of their complex combinatorial nature.
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We would like to thank E. Furlong (European Molecular Biology Laboratory (EMBL)) and M. Levine (University of California Berkeley) for generously providing Twist antibodies; B. Dickson, W. Lugmayr, R. Revilla (IMP), C. Schlötterer (University of Veterinary Medicine Vienna), M. Levine (University of California Berkeley) and R. Krumlauf (Stowers Institute for Medical Research) for discussions, help and advice. A.F.B. was supported by the Austrian Ministry for Science and Research through the Genome Research in Austria (GEN-AU) Bioinformatics Integration Network III. J.Z. is a Pew scholar. A.S. is supported by an European Research Council (ERC) Starting Grant from the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 242922.
The authors declare no competing financial interests.
Supplementary Figures 1–19 and Supplementary Tables 1–6, 8–10 and 14–16. (PDF 2930 kb)
Conservation of D. melanosgaster Twist binding peaks in six Drosophila species (XLS 390 kb)
Quantitative changes of Twist binding peaks in all six Drosophila species (XLS 2360 kb)
GO analysis of invariant vs. variant peaks (XLS 446 kb)
GO analysis of genes near Twist binding peaks (XLS 588 kb)
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He, Q., Bardet, A., Patton, B. et al. High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species. Nat Genet 43, 414–420 (2011). https://doi.org/10.1038/ng.808
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