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

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  • Ines Desanlis

    (Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
    Université de Montréal)

  • Yacine Kherdjemil

    (Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
    Université de Montréal
    EMBL Heidelberg, Meyerhofstrasse 1)

  • Alexandre Mayran

    (Molecular Genetics Research Unit, Institut de Recherches Cliniques de Montréal
    EPFL, School of Life Sciences)

  • 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
    McGill University
    Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue)

  • Rushikesh Sheth

    (University of Basel)

  • Rolf Zeller

    (University of Basel)

  • Jacques Drouin

    (Université de Montréal
    Molecular Genetics Research Unit, Institut de Recherches Cliniques de Montréal)

  • Marie Kmita

    (Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal
    Université de Montréal
    McGill University)

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.

Suggested Citation

  • Ines Desanlis & Yacine Kherdjemil & Alexandre Mayran & Yasser Bouklouch & Claudia Gentile & Rushikesh Sheth & Rolf Zeller & Jacques Drouin & Marie Kmita, 2020. "HOX13-dependent chromatin accessibility underlies the transition towards the digit development program," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16317-2
    DOI: 10.1038/s41467-020-16317-2
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    Cited by:

    1. Aiko Kawasumi-Kita & Sang-Woo Lee & Daisuke Ohtsuka & Kaori Niimi & Yoshifumi Asakura & Keiichi Kitajima & Yuto Sakane & Koji Tamura & Haruki Ochi & Ken-ichi T. Suzuki & Yoshihiro Morishita, 2024. "hoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Christopher Chase Bolt & Lucille Lopez-Delisle & Aurélie Hintermann & Bénédicte Mascrez & Antonella Rauseo & Guillaume Andrey & Denis Duboule, 2022. "Context-dependent enhancer function revealed by targeted inter-TAD relocation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Viviane Tran & Sarah Nahlé & Amélie Robert & Inès Desanlis & Ryan Killoran & Sophie Ehresmann & Marie-Pier Thibault & David Barford & Kodi S. Ravichandran & Martin Sauvageau & Matthew J. Smith & Marie, 2022. "Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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