RT Journal Article
SR Electronic
T1 The Hox transcription factor Ubx ensures somatic myogenesis by suppressing the mesodermal master regulator Twist
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.24.963231
DO 10.1101/2020.02.24.963231
A1 Katrin Domsch
A1 Julia Schröder
A1 Matthias Janeschik
A1 Christoph Schaub
A1 Ingrid Lohmann
YR 2020
UL http://biorxiv.org/content/early/2020/02/25/2020.02.24.963231.abstract
AB Early determination factors and lineage-specific master regulators are essential for the specification of cell and tissue types. However, once a cell has committed to a specific fate, it is equally critical to restrict the activity of such factors to enable proper differentiation. In many studies the functional network for master regulators are under constant investigations. Yet, how these factors are silenced remains unclear. Using the Drosophila mesoderm as a model and a comparative genomic approach, we identified the Hox transcription factor (TF) Ultrabithorax (Ubx) to be critical for the repression of the mesodermal master regulator Twist (Twi). Mesoderm-specific Ubx loss-of-function experiments using CRISPR/Cas9 as well as overexpression experiments demonstrated that Ubx majorly impacts twi transcription. A detailed mechanistic analysis revealed that Ubx requires the function of the NK-homeodomain protein Tinman (Tin) but not the muscle differentiation factor Myocyte enhancer factor 2 (Mef2) to bind to the twi promoter. Furthermore, we found these TF interactions to be critical for silencing of the twi promoter region by recruiting the Polycomb DNA binding protein Pleiohomeotic (Pho). In sum, our study demonstrates that the Hox TF Ubx is a critical player in mediating the silencing of the mesodermal master regulator Twi, which is crucial for coordinated muscle differentiation.