Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities

• Verfasst von: Pinto, Pedro [VerfasserIn]
• Verfasst von: Domsch, Katrin [VerfasserIn]
• Verfasst von: Gao, Xuefan [VerfasserIn]
• Verfasst von: Wölk, Michaela [VerfasserIn]
• Verfasst von: Carnesecchi, Julie [VerfasserIn]
• Verfasst von: Lohmann, Ingrid [VerfasserIn]
• Titel: Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities
• Verf.angabe: Pedro B. Pinto, Katrin Domsch, Xuefan Gao, Michaela Wölk, Julie Carnesecchi & Ingrid Lohmann
• E-Jahr: 2022
• Jahr: 26 August 2022
• Umfang: 17 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 27.10.2022
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Nature Publishing Group UK, 2010
• Jahr Quelle: 2022
• Band/Heft Quelle: 13(2022), Artikel-ID 5037, Seite 1-17
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/s41467-022-32408-8
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Morphogenesis
• Sach-SW: Pattern formation
• Sach-SW: Transcriptional regulatory elements
• K10plus-PPN: 1820223388
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.