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A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm

Author

Listed:
  • Luca Mariani

    (University of Copenhagen)

  • Xiaogang Guo

    (University of Copenhagen)

  • Niels Alvaro Menezes

    (University of Copenhagen)

  • Anna Maria Drozd

    (University of Copenhagen)

  • Selgin Deniz Çakal

    (University of Copenhagen)

  • Qinhu Wang

    (Northwest A&F University)

  • Elisabetta Ferretti

    (University of Copenhagen)

Abstract

One fundamental yet unresolved question in biology remains how cells interpret the same signalling cues in a context-dependent manner resulting in lineage specification. A key step for decoding signalling cues is the establishment of a permissive chromatin environment at lineage-specific genes triggering transcriptional responses to inductive signals. For instance, bipotent neuromesodermal progenitors (NMPs) are equipped with a WNT-decoding module, which relies on TCFs/LEF activity to sustain both NMP expansion and paraxial mesoderm differentiation. However, how WNT signalling activates lineage specific genes in a temporal manner remains unclear. Here, we demonstrate that paraxial mesoderm induction relies on the TALE/HOX combinatorial activity that simultaneously represses NMP genes and activates the differentiation program. We identify the BRACHYURY-TALE/HOX code that destabilizes the nucleosomes at WNT-responsive regions and establishes the permissive chromatin landscape for de novo recruitment of the WNT-effector LEF1, unlocking the WNT-mediated transcriptional program that drives NMPs towards the paraxial mesodermal fate.

Suggested Citation

  • Luca Mariani & Xiaogang Guo & Niels Alvaro Menezes & Anna Maria Drozd & Selgin Deniz Çakal & Qinhu Wang & Elisabetta Ferretti, 2021. "A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25370-4
    DOI: 10.1038/s41467-021-25370-4
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    Cited by:

    1. Marta Losa & Iros Barozzi & Marco Osterwalder & Viviana Hermosilla-Aguayo & Angela Morabito & Brandon H. Chacón & Peyman Zarrineh & Ausra Girdziusaite & Jean Denis Benazet & Jianjian Zhu & Susan Macke, 2023. "A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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