1. A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm.
- Author
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Mariani L, Guo X, Menezes NA, Drozd AM, Çakal SD, Wang Q, and Ferretti E
- Subjects
- Animals, Cell Differentiation, Cell Lineage, Fetal Proteins genetics, Gene Expression Regulation, Developmental, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Mesoderm embryology, Mice, Mice, Knockout, Neural Stem Cells cytology, Nucleosomes genetics, Nucleosomes metabolism, T-Box Domain Proteins genetics, Fetal Proteins metabolism, Mesoderm metabolism, Multigene Family, Neural Stem Cells metabolism, T-Box Domain Proteins metabolism, Wnt Signaling Pathway
- 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., (© 2021. The Author(s).)
- Published
- 2021
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