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The Hox Transcription Factor Ubx Ensures Somatic Myogenesis by Suppressing the Mesodermal Master Regulator Twist

Katrin Domsch1, Julia Schröder1, Matthias Janeschik1

  • 1Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, 69120 Heidelberg, Germany.

Cell Reports
|January 6, 2021
PubMed

Insights

The Hox transcription factor Ultrabithorax (Ubx) silences the master regulator Twist in Drosophila mesoderm. This repression, mediated by Tinman and Pleiohomeotic, is crucial for muscle cell differentiation.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Master regulators control cell-type specification but must be silenced for differentiation.
  • Mechanisms of silencing lineage-specific transcription factors remain largely unknown.

Purpose of the Study:

  • To investigate how master regulators like Twist are silenced after cell fate commitment.
  • To identify the factors and mechanisms involved in repressing Twist transcription in the Drosophila mesoderm.

Main Methods:

  • Comparative genomics to identify candidate repressors.
  • Drosophila mesoderm model system.
  • CRISPR-Cas9 for loss-of-function studies.
  • Overexpression studies.
  • Mechanistic analysis of protein-DNA interactions and recruitment of silencing factors.

Main Results:

  • Identified Ultrabithorax (Ubx) as a key repressor of the Twist master regulator.
  • Demonstrated that Ubx directly impacts twist transcription in mesodermal cells.
  • Revealed that Ubx requires the NK-homeodomain protein Tinman for binding to the twist promoter.
  • Showed that Ubx-Tinman interaction recruits the Polycomb protein Pleiohomeotic to silence Twist.

Conclusions:

  • Ubx acts as a critical mediator in silencing Twist transcription.
  • The Ubx-Tinman-Pleiohomeotic complex is essential for repressing Twist.
  • This silencing mechanism is vital for coordinated muscle differentiation in Drosophila.
Keywords:
Hox genesMef2TinmanUltrabithorax (Ubx)mesodermrepressiontwist

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