Cited by 210Muscle Physiology and DisordersDevelopmental Biology and Gene RegulationCongenital heart defects research

Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

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Messina, Graziella, Biressi, Stefano, Monteverde, Stefania, Magli, Alessandro, Cassano, Marco, Perani, Laura, Roncaglia, Elena, Tagliafico, Enrico +6 more·2010·Cell

Abstract

Skeletal myogenesis, like hematopoiesis, occurs in successive developmental stages that involve different cell populations and expression of different genes. We show here that the transcription factor nuclear factor one X (Nfix), whose expression is activated by Pax7 in fetal muscle, in turn activates the transcription of fetal specific genes such as MCK and beta-enolase while repressing embryonic genes such as slow myosin. In the case of the MCK promoter, Nfix forms a complex with PKC theta that binds, phosphorylates, and activates MEF2A. Premature expression of Nfix activates fetal and suppresses embryonic genes in embryonic muscle, whereas muscle-specific ablation of Nfix prevents fetal and maintains embryonic gene expression in the fetus. Therefore, Nfix acts as a transcriptional switch from embryonic to fetal myogenesis.

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Crossref · 10.1016/j.cell.2010.01.027

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  • Although their loci are not very near to each other, Nfia, Nfib and Nfix regulate cell-type differentiation in many tissues, function as homo- or heterodimers, and bind to largely common targets.

    “Although their loci are not very near to each other, Nfia, Nfib and Nfix regulate cell-type differentiation in many tissues94–96, function as homo- or heterodimers, and bind to largely common targets97.”

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Authors
Messina, G., Biressi, S., Monteverde, S., Magli, A., Cassano, M., Perani, L., Roncaglia, E., Tagliafico, E., Starnes, L., Campbell, C. E., Grossi, M., Goldhamer, D. J., Gronostajski, R. M., & Cossu, G.
Affiliations
  • University of Milan (IT)
  • Stanford Medicine (US)
  • IRCCS Ospedale San Raffaele (IT)
  • University of Modena and Reggio Emilia (IT)
  • Leuven Stem Cell Institute (BE)
  • Sapienza University of Rome (IT)
  • University at Buffalo, State University of New York (US)
  • University of Connecticut (US)
Corresponding author
Cossu, Giulio
Venue
Cell
Publisher
Elsevier BV
Published
2010-02
Volume
140
Issue
4
Pages
554-566
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2163361011
Cited by
210
References
41
Citations by year
2026: 5 · 2025: 11 · 2024: 9 · 2023: 21 · 2022: 16 · 2021: 12 · 2020: 20 · 2019: 11 · 2018: 18 · 2017: 13 · 2016: 8 · 2015: 16 · 2014: 15 · 2013: 14 · 2012: 11
FWCI
4.56
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Iris (University of Trento) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Funders
  • U.S. Public Health Service (H080624)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR052777, R01AR052777)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
NFIX, skeletal myogenesis, fetal muscle, embryonic muscle, Pax7, beta-enolase, slow myosin, MEF2A, PKC theta, transcriptional switch, gene expression regulation, skeletal muscle development
MeSH terms
Protein Kinase C-theta, Animals, Fetus, Humans, Isoenzymes, Phosphopyruvate Hydratase, Protein Kinase C, Transcription, Genetic, Myogenic Regulatory Factors, Muscle, Skeletal, Gene Expression Regulation, Developmental, Muscle Development, NFATC Transcription Factors, Mice, PAX7 Transcription Factor, NFI Transcription Factors, MEF2 Transcription Factors

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