The expression of NF-YA, the DNA-binding subunit of the CCAAT-binding transcription factor NF-Y, is down-regulated in adult skeletal muscle to allow a complete terminal differentiation. The NF-YA gene encodes for two alternative splice variants, NF-YAs and NF-YAl: in human haematopoietic and mouse embryonic stem cells, the expression of NF-YAs or NF-YAl is crucial to promote proliferation or differentiation, respectively. The role of NF-YA isoforms in skeletal myogenesis and satellite cells fate has never been investigated. Here we show that both NF-YA isoforms are induced in mouse regenerating muscle and are expressed in satellite cells (SCs). The abrogation of NF-Y activity impairs both proliferation and differentiation of SCs. Forced expression of NF-YAs stimulates SCs proliferation, while NF-YAl enhances their differentiation. The same effects are observed in mouse C2C12 myoblasts, in which the two isoforms activate opposite transcriptional programs. NF-YAs upregulates genes annotated in growth factor binding, cell adhesion and extra cellular matrix Gene Onthology terms, while NF-YAl increases the transcription of genes belonging to sarcomere, muscle cell differentiation, development and muscle contraction categories. NF-YAl boosts myoblasts differentiation by up-regulating the transcription of novel NF-Y target genes, among which Mef2D, Six4 and Cdkn1C, which are known to be involved in the differentiation program. Overall, our results highlight the functional difference between NF-YA isoforms, whose modulation could be useful to improve stem cell based therapies to treat muscular dystrophy.

Role of the CCAAT-transcription factor NF-Y and its splice variants in myogenic differentiation and muscle regeneration / Basile, Valentina; Baruffaldi, Fiorenza; Laura, Ricci; Molinari, Susanna; Imbriano, Carol. - (2016). ((Intervento presentato al convegno Myology 2016 - 5th International Congress of Myology tenutosi a Lyon nel 14/03/2016.

Role of the CCAAT-transcription factor NF-Y and its splice variants in myogenic differentiation and muscle regeneration

BASILE, Valentina;BARUFFALDI, Fiorenza;MOLINARI, Susanna;IMBRIANO, Carol
2016

Abstract

The expression of NF-YA, the DNA-binding subunit of the CCAAT-binding transcription factor NF-Y, is down-regulated in adult skeletal muscle to allow a complete terminal differentiation. The NF-YA gene encodes for two alternative splice variants, NF-YAs and NF-YAl: in human haematopoietic and mouse embryonic stem cells, the expression of NF-YAs or NF-YAl is crucial to promote proliferation or differentiation, respectively. The role of NF-YA isoforms in skeletal myogenesis and satellite cells fate has never been investigated. Here we show that both NF-YA isoforms are induced in mouse regenerating muscle and are expressed in satellite cells (SCs). The abrogation of NF-Y activity impairs both proliferation and differentiation of SCs. Forced expression of NF-YAs stimulates SCs proliferation, while NF-YAl enhances their differentiation. The same effects are observed in mouse C2C12 myoblasts, in which the two isoforms activate opposite transcriptional programs. NF-YAs upregulates genes annotated in growth factor binding, cell adhesion and extra cellular matrix Gene Onthology terms, while NF-YAl increases the transcription of genes belonging to sarcomere, muscle cell differentiation, development and muscle contraction categories. NF-YAl boosts myoblasts differentiation by up-regulating the transcription of novel NF-Y target genes, among which Mef2D, Six4 and Cdkn1C, which are known to be involved in the differentiation program. Overall, our results highlight the functional difference between NF-YA isoforms, whose modulation could be useful to improve stem cell based therapies to treat muscular dystrophy.
Myology 2016 - 5th International Congress of Myology
Lyon
14/03/2016
Basile, Valentina; Baruffaldi, Fiorenza; Laura, Ricci; Molinari, Susanna; Imbriano, Carol
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1107130
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