PLoS biology, 2019-02, Vol.17 (2), p.e3000153-e3000153
2019
Details
- Autor(en) / Beteiligte
- Titel
- Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mesoderm
- Ist Teil von
- PLoS biology, 2019-02, Vol.17 (2), p.e3000153-e3000153
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The transcriptional mechanisms driving lineage specification during development are still largely unknown, as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors-mesogenin 1 (Msgn1), T-box 6 (Tbx6), forkhead box C1 (Foxc1), paired box 3 (Pax3), Paraxis, mesenchyme homeobox 1 (Meox1), sine oculis-related homeobox 1 (Six1), and myogenic factor 5 (Myf5)-in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage. By assaying chromatin accessibility, genomic binding and transcription profiling in mesodermal cells from mouse and human Pax3-induced embryonic stem cells and Pax3-null embryonic day (E)9.5 mouse embryos, we identified conserved Pax3 functions in the activation of the skeletal myogenic lineage through modulation of Hedgehog, Notch, and bone morphogenetic protein (BMP) signaling pathways. In addition, we demonstrate that Pax3 molecular function involves chromatin remodeling of its bound elements through an increase in chromatin accessibility and cooperation with sine oculis-related homeobox 4 (Six4) and TEA domain family member 2 (Tead2) factors. To our knowledge, these data provide the first integrated analysis of Pax3 function, demonstrating its ability to remodel chromatin in mesodermal cells from developing embryos and proving a mechanistic footing for the transcriptional hierarchy driving myogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1545-7885, 1544-9173eISSN: 1545-7885DOI: 10.1371/journal.pbio.3000153Titel-ID: cdi_plos_journals_2249959834
- Format
- –
- Schlagworte
- Accessibility, Animals, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, Bioinformatics, Biology and Life Sciences, Bone morphogenetic proteins, Cell Differentiation, Cell Line, Chromatin Assembly and Disassembly, Chromatin remodeling, Cooperation, Deoxyribonucleic acid, DNA, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Embryo cells, Embryo, Mammalian, Embryonic Stem Cells - cytology, Embryonic Stem Cells - metabolism, Embryos, Forkhead protein, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, Funding, Gene expression, Gene Expression Regulation, Developmental, Genomes, Genomics, Heart, Homeobox, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Humans, Laboratories, Medicine, Mesenchyme, Mesoderm, Mesoderm - cytology, Mesoderm - growth & development, Mesoderm - metabolism, Mice, Mice, Transgenic, Muscle Cells - cytology, Muscle Cells - metabolism, Muscle Development - genetics, Muscle, Skeletal - cytology, Muscle, Skeletal - growth & development, Muscle, Skeletal - metabolism, Myogenesis, Myogenic Regulatory Factor 5 - genetics, Myogenic Regulatory Factor 5 - metabolism, Pax3 protein, PAX3 Transcription Factor - genetics, PAX3 Transcription Factor - metabolism, Signal Transduction, SIX gene family, Stem cell transplantation, Stem cells, Supervision, T-Box Domain Proteins, TEA Domain Transcription Factors, Time dependence, Trans-Activators - genetics, Trans-Activators - metabolism, Transcription factors, Transcription Factors - genetics, Transcription Factors - metabolism