MLL1 is required for PAX7 expression and satellite cell self-renewal in mice
| Autor: | Michael A. Rudnicki, Caroline E. Brun, Christopher J. Porter, Marie-Claude Sincennes, A. Francis Stewart, John Saber, Patricia Ernst, Gregory C. Addicks |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Molecular biology General Physics and Astronomy Stem cells Myoblasts Mice 0302 clinical medicine Myocyte Promoter Regions Genetic lcsh:Science Cells Cultured Mice Knockout Multidisciplinary PAX7 Transcription Factor Cell Differentiation musculoskeletal system Cell biology medicine.anatomical_structure Epigenetics Female MYF5 Myogenic Regulatory Factor 5 Stem cell Cell activation Transcription tissues Myeloid-Lymphoid Leukemia Protein animal structures Satellite Cells Skeletal Muscle Science Biology Methylation Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Transcription factor Cell Proliferation Cell growth Skeletal muscle Promoter Histone-Lysine N-Methyltransferase General Chemistry Mice Inbred C57BL 030104 developmental biology lcsh:Q 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | PAX7 is a paired-homeobox transcription factor that specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. We previously found that PAX7 recruits the H3K4 methyltransferases MLL1/2 to epigenetically activate target genes. Here we report that in the absence of Mll1, myoblasts exhibit reduced H3K4me3 at both Pax7 and Myf5 promoters and reduced Pax7 and Myf5 expression. Mll1-deficient myoblasts fail to proliferate but retain their differentiation potential, while deletion of Mll2 had no discernable effect. Re-expression of PAX7 in committed Mll1 cKO myoblasts restored H3K4me3 enrichment at the Myf5 promoter and Myf5 expression. Deletion of Mll1 in satellite cells reduced satellite cell proliferation and self-renewal, and significantly impaired skeletal muscle regeneration. Pax7 expression was unaffected in quiescent satellite cells but was markedly downregulated following satellite cell activation. Therefore, MLL1 is required for PAX7 expression and satellite cell function in vivo. Furthermore, PAX7, but not MLL1, is required for Myf5 transcriptional activation in committed myoblasts. PAX7 transcription factor specifies the myogenic identity of muscle stem cells and acts as a nodal factor by stimulating proliferation while inhibiting differentiation. Here authors find that Mll1 deletion in myoblasts in mice results in reduced H3K4me3 at both Pax7 and Myf5 promoters, reduced Pax7 and Myf5 expression, and proliferation defects. |
| Databáze: | OpenAIRE |
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