Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities
Hox proteins have similar binding specificities in vitro, yet they control different morphologies in vivo. This paradox has been partially solved with the identification of Hox low-affinity binding sites. However, anterior Hox proteins are more promiscuous than posterior Hox proteins, raising the qu...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
26 August 2022
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| In: |
Nature Communications
Year: 2022, Jahrgang: 13, Pages: 1-17 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-32408-8 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-022-32408-8 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-022-32408-8 |
| Verfasserangaben: | Pedro B. Pinto, Katrin Domsch, Xuefan Gao, Michaela Wölk, Julie Carnesecchi & Ingrid Lohmann |
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| 520 | |a Hox proteins have similar binding specificities in vitro, yet they control different morphologies in vivo. This paradox has been partially solved with the identification of Hox low-affinity binding sites. However, anterior Hox proteins are more promiscuous than posterior Hox proteins, raising the question how anterior Hox proteins achieve specificity. We use the AP2x enhancer, which is activated in the maxillary head segment by the Hox TF Deformed (Dfd). This enhancer lacks canonical Dfd-Exd sites but contains several predicted low-affinity sites. Unexpectedly, these sites are strongly bound by Dfd-Exd complexes and their conversion into optimal Dfd-Exd sites results only in a modest increase in binding strength. These small variations in affinity change the sensitivity of the enhancer to different Dfd levels, resulting in perturbed AP-2 expression and maxillary morphogenesis. Thus, Hox-regulated morphogenesis seems to result from the co-evolution of Hox binding affinity and Hox dosage for precise target gene regulation. | ||
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| 650 | 4 | |a Pattern formation | |
| 650 | 4 | |a Transcriptional regulatory elements | |
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