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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Myogenesis control by SIX transcriptional complexes.

Pascal Maire1, Matthieu Dos Santos1, Rouba Madani1

  • 1Université de Paris, Institut Cochin, INSERM, CNRS, 75014, Paris, France.

Seminars in Cell & Developmental Biology
|April 6, 2020
PubMed
Summary

SIX homeoproteins are crucial for muscle development and function in vertebrates. These proteins regulate gene expression, influencing muscle formation, contraction, and diversity from embryo to adult stages.

Keywords:
Adult myofiberDevelopmentGenetic networkMyoDMyogenesisMyogeninPax7Satellite cellSix1

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • SIX homeoproteins were initially identified in Drosophila, participating in the Pax-Six-Eya-Dach (PSED) network essential for eye development.
  • The PSED network and SIX proteins' roles in vertebrate muscle formation have been subsequently elucidated.
  • Evolutionarily conserved interactions with EYA and DACH proteins are fundamental to SIX transcriptional complexes (STC) in both embryonic and adult muscle.

Purpose of the Study:

  • To investigate the comprehensive role of SIX homeoproteins in vertebrate muscle development and function.
  • To understand the regulatory mechanisms employed by SIX proteins throughout myogenesis and in adult myofibers.
  • To explore the involvement of SIX proteins in myofiber diversity and maintenance.

Main Methods:

  • Analysis of SIX gene expression patterns during muscle development (embryonic and adult stages).
  • In vivo studies to assess the functional impact of SIX proteins on myogenic fate acquisition and adult myofiber properties.
  • Examination of gene expression regulated by SIX proteins, including those involved in metabolism, sarcomeric organization, and calcium homeostasis.

Main Results:

  • SIX genes are expressed across various muscle cell types, including proliferating stem cells and post-mitotic myofibers.
  • SIX proteins act through feedforward mechanisms to control myogenic regulatory factors during embryogenesis.
  • In adult myofibers, SIX proteins regulate genes critical for contraction, relaxation, fatigability, metabolism, sarcomeric organization, and calcium homeostasis.

Conclusions:

  • SIX homeoproteins are vital regulators of muscle development and function in vertebrates.
  • SIX proteins orchestrate key events in myogenesis and maintain adult myofiber characteristics.
  • SIX proteins contribute significantly to the diversity and maintenance of myofiber types throughout life.