HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

Ines Desanlis, Yacine Kherdjemil, Alexandre Mayran, Yasser Bouklouch, Claudia Gentile, Rushikesh Sheth, Rolf Zeller, Jacques Drouin and Marie Kmita ()
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Ines Desanlis: Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
Yacine Kherdjemil: Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
Alexandre Mayran: Molecular Genetics Research Unit, Institut de Recherches Cliniques de Montréal
Yasser Bouklouch: Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
Claudia Gentile: Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
Rushikesh Sheth: University of Basel
Rolf Zeller: University of Basel
Jacques Drouin: Université de Montréal
Marie Kmita: Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Hox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromatin context on HOX binding specificity remains elusive. Here, we used the developing limb as a model system to compare the binding specificity of HOXA13 and HOXD13 (HOX13 hereafter), which are required for digit formation, and HOXA11, involved in forearm/leg development. We find that upon ectopic expression in distal limb buds, HOXA11 binds sites normally HOX13-specific. Importantly, these sites are loci whose chromatin accessibility relies on HOX13. Moreover, we show that chromatin accessibility specific to the distal limb requires HOX13 function. Based on these results, we propose that HOX13 TFs pioneer the distal limb-specific chromatin accessibility landscape for the proper implementation of the distal limb developmental program.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16317-2

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DOI: 10.1038/s41467-020-16317-2

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