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

• Published in: Molecular biology of the cell 2003-07, Vol.14 (7), p.2706-2715
• Main Authors: Gurtner, Aymone, Manni, Isabella, Fuschi, Paola, Mantovani, Roberto, Guadagni, Fiorella, Sacchi, Ada, Piaggio, Giulia
• Format: Article
• Language: English
• Subjects: Animals; CCAAT-Binding Factor - metabolism; Cell Cycle; Cell Differentiation; Cell Nucleus - metabolism; Cells, Cultured; Cyclin A - metabolism; Cyclin B - metabolism; Cyclin-Dependent Kinases - metabolism; Down-Regulation; Gene Expression Regulation; Mice; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - metabolism; Promoter Regions, Genetic; Protein Subunits - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e02-09-0600

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.