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The L27 domain of MPP7 enhances TAZ-YY1 cooperation to renew muscle stem cells

  • 0Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD, 21218, USA.
Embo Reports +

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November 4, 2024

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November 4, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

MPP7 and AMOT proteins regulate skeletal muscle stem cell (MuSC) renewal by coordinating transcriptional programs. This interaction enhances gene expression crucial for maintaining muscle regenerative capacity.

Area Of Science

  • Molecular biology
  • Cell biology
  • Regenerative medicine

Background

  • Stem cells are crucial for tissue repair and regeneration.
  • Skeletal muscle stem cells (MuSCs) possess self-renewal capacity for lifelong regeneration.
  • Transcriptional co-factors TAZ/YAP and YY1 regulate key aspects of MuSC function.

Purpose Of The Study

  • To investigate the molecular mechanisms governing skeletal muscle stem cell (MuSC) renewal during regeneration.
  • To identify novel protein interactions and regulatory pathways involved in MuSC self-renewal.

Main Methods

  • Investigated the roles of MPP7 and AMOT in MuSC renewal.
  • Analyzed the interaction between MPP7, AMOT, TAZ/YAP, and YY1.
  • Examined gene regulation at promoter regions using co-occupancy studies.
  • Assessed the impact of protein interactions on transcriptional activity.

Main Results

  • MPP7 and AMOT collaborate with TAZ/YAP and YY1 to regulate common target genes.
  • The L27 domain of MPP7 potentiates TAZ/YAP and YY1 interactions and activity.
  • AMOT functions as a molecular bridge between MPP7, TAZ/YAP, and YY1.
  • MPP7, TAZ, and YY1 co-occupy the promoters of key renewal genes like Carm1.
  • Carm1 is identified as a critical regulator of MuSC renewal.

Conclusions

  • A novel renewal program for skeletal muscle stem cells (MuSCs) is defined, involving coordinated transcriptional regulation.
  • Protein-protein interactions mediated by MPP7 and AMOT are essential for activating specific gene programs required for MuSC self-renewal.
  • This study elucidates a complex regulatory network critical for maintaining muscle regenerative potential.

Keywords:

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