Requirement for down-regulation of the CCAAT-binding activity of the NF-Y transcription factor during skeletal muscle differentiation

Aymone Gurtner, Isabella Manni, Paola Fuschi, Roberto Mantovani, Fiorella Guadagni, Ada Sacchi, Giulia Piaggio

Research output: Contribution to journalArticle

Abstract

NF-Y is composed of three subunits, NF-YA, NF-YB, and NF-YC, all required for DNA binding. All subunits are expressed in proliferating skeletal muscle cells, whereas NF-YA alone is undetectable in terminally differentiated cells in vitro. By immunohistochemistry, we show that the NF-YA protein is not expressed in the nuclei of skeletal and cardiac muscle cells in vivo. By chromatin immunoprecipitation experiments, we demonstrate herein that NF-Y does not bind to the CCAAT boxes of target promoters in differentiated muscle cells. Consistent with this, the activity of these promoters is down-regulated in differentiated muscle cells. Finally, forced expression of the NF-YA protein in cells committed to differentiate leads to an impairment in the down-regulation of cyclin A, cyclin B1, and cdk1 expression and is accompanied by a delay in myogenin expression. Thus, our results indicate that the suppression of NF-Y function is of crucial importance for the inhibition of several cell cycle genes and the induction of the early muscle-specific program in postmitotic muscle cells.

Original languageEnglish
Pages (from-to)2706-2715
Number of pages10
JournalMolecular Biology of the Cell
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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