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

Luca Mariani, Xiaogang Guo, Niels Alvaro Menezes, Anna Maria Drozd, Selgin Deniz Çakal, Qinhu Wang and Elisabetta Ferretti ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25370-4

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DOI: 10.1038/s41467-021-25370-4

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