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Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis.
FASEB J. 2015 Nov; 29(11):4738-55.FJ

Abstract

Adult skeletal muscles can regenerate after injury, due to the presence of satellite cells, a quiescent population of myogenic progenitor cells. Once activated, satellite cells repair the muscle damage by undergoing myogenic differentiation. The myogenic regulatory factors (MRFs) coordinate the process of progenitor differentiation in cooperation with other families of transcription factors (TFs). The Six1 and Six4 homeodomain TFs are expressed in developing and adult muscle and Six1 is critical for embryonic and adult myogenesis. However, the lack of a muscle developmental phenotype in Six4-null mice, which has been attributed to compensation by other Six family members, has discouraged further assessment of the role of Six4 during adult muscle regeneration. By employing genome-wide approaches to address the function of Six4 during adult skeletal myogenesis, we have identified a core set of muscle genes coordinately regulated in adult muscle precursors by Six4 and the MRF MyoD. Throughout the genome of differentiating adult myoblasts, the cooperation between Six4 and MyoD is associated with chromatin repressive mark removal by Utx, a demethylase of histone H3 trimethylated at lysine 27. Among the genes coordinately regulated by Six4 and MyoD are several genes critical for proper in vivo muscle regeneration, implicating a role of Six4 in this process. Using in vivo RNA interference of Six4, we expose an uncompensated function of this TF during muscle regeneration. Together, our results reveal a role for Six4 during adult muscle regeneration and suggest a widespread mechanism of cooperation between Six4 and MyoD.

Authors+Show Affiliations

*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.*Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada; and Department of Biochemistry, Microbiology, and Immunology and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada alexandre.blais@uottawa.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26229056

Citation

Chakroun, Imane, et al. "Genome-wide Association Between Six4, MyoD, and the Histone Demethylase Utx During Myogenesis." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 29, no. 11, 2015, pp. 4738-55.
Chakroun I, Yang D, Girgis J, et al. Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis. FASEB J. 2015;29(11):4738-55.
Chakroun, I., Yang, D., Girgis, J., Gunasekharan, A., Phenix, H., Kærn, M., & Blais, A. (2015). Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 29(11), 4738-55. https://doi.org/10.1096/fj.15-277053
Chakroun I, et al. Genome-wide Association Between Six4, MyoD, and the Histone Demethylase Utx During Myogenesis. FASEB J. 2015;29(11):4738-55. PubMed PMID: 26229056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis. AU - Chakroun,Imane, AU - Yang,Dabo, AU - Girgis,John, AU - Gunasekharan,Atchayaa, AU - Phenix,Hilary, AU - Kærn,Mads, AU - Blais,Alexandre, Y1 - 2015/07/30/ PY - 2015/06/11/received PY - 2015/07/20/accepted PY - 2015/8/1/entrez PY - 2015/8/1/pubmed PY - 2016/2/13/medline KW - adult muscle regeneration KW - histone methylation KW - transcriptional regulation SP - 4738 EP - 55 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 29 IS - 11 N2 - Adult skeletal muscles can regenerate after injury, due to the presence of satellite cells, a quiescent population of myogenic progenitor cells. Once activated, satellite cells repair the muscle damage by undergoing myogenic differentiation. The myogenic regulatory factors (MRFs) coordinate the process of progenitor differentiation in cooperation with other families of transcription factors (TFs). The Six1 and Six4 homeodomain TFs are expressed in developing and adult muscle and Six1 is critical for embryonic and adult myogenesis. However, the lack of a muscle developmental phenotype in Six4-null mice, which has been attributed to compensation by other Six family members, has discouraged further assessment of the role of Six4 during adult muscle regeneration. By employing genome-wide approaches to address the function of Six4 during adult skeletal myogenesis, we have identified a core set of muscle genes coordinately regulated in adult muscle precursors by Six4 and the MRF MyoD. Throughout the genome of differentiating adult myoblasts, the cooperation between Six4 and MyoD is associated with chromatin repressive mark removal by Utx, a demethylase of histone H3 trimethylated at lysine 27. Among the genes coordinately regulated by Six4 and MyoD are several genes critical for proper in vivo muscle regeneration, implicating a role of Six4 in this process. Using in vivo RNA interference of Six4, we expose an uncompensated function of this TF during muscle regeneration. Together, our results reveal a role for Six4 during adult muscle regeneration and suggest a widespread mechanism of cooperation between Six4 and MyoD. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/26229056/Genome_wide_association_between_Six4_MyoD_and_the_histone_demethylase_Utx_during_myogenesis_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.15-277053?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -