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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Phenotypic transcription factors epigenetically mediate cell growth control

Syed A Ali1, Sayyed K Zaidi, Caroline S Dacwag

  • 1Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 1, 2008
PubMed

Insights

Cell fate factors suppress ribosomal RNA (rRNA) genes during differentiation. This epigenetic control mechanism coordinates cell growth with phenotype commitment.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Ribosomal RNA (rRNA) gene expression is downregulated during cell differentiation processes like osteogenesis, myogenesis, and adipogenesis.
  • Understanding the mechanisms linking growth control and cell fate commitment is crucial.

Purpose of the Study:

  • To investigate how cell fate-determining factors regulate rRNA gene expression during lineage progression.
  • To elucidate the interplay between growth control and phenotype commitment.

Main Methods:

  • Chromatin immunoprecipitation to assess factor occupancy at rDNA loci.
  • RNA interference and ectopic expression studies to determine functional roles.
  • Analysis of interactions with upstream binding factor (UBF-1) at nucleoli.

Main Results:

  • Cell fate factors (MyoD, myogenin, Runx2, C/EBPbeta) bind to rDNA loci and suppress rRNA expression.
  • This suppression is accompanied by decreased rRNA expression and reduced occupancy by c-Myc.
  • Phenotypic factors interact with UBF-1, an interaction maintained epigenetically on mitotic chromosomes.

Conclusions:

  • Lineage-specific differentiation factors epigenetically control ribosomal biogenesis.
  • This mechanism coordinates cell growth with phenotype commitment during development.
  • Suppression of rRNA genes and protein synthesis by differentiation factors is a general developmental mechanism.

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