title: G1/S Inhibitors and the SWI/SNF Complex Control Cell-Cycle Exit during Muscle Differentiation.
abstract: The transition from proliferating precursor cells to post-mitotic differentiated cells is crucial for development, tissue homeostasis, and tumor suppression. To study cell-cycle exit during differentiation in vivo, we developed a conditional knockout and lineage-tracing system for Caenorhabditis elegans. Combined lineage-specific gene inactivation and genetic screening revealed extensive redundancies between previously identified cell-cycle inhibitors and the SWI/SNF chromatin-remodeling complex. Muscle precursor cells missing either SWI/SNF or G1/S inhibitor function could still arrest cell division, while simultaneous inactivation of these regulators caused continued proliferation and a C. elegans tumor phenotype. Further genetic analyses support that SWI/SNF acts in concert with hlh-1 MyoD, antagonizes Polycomb-mediated transcriptional repression, and suppresses cye-1 Cyclin E transcription to arrest cell division of muscle precursors. Thus, SWI/SNF and G1/S inhibitors provide alternative mechanisms to arrest cell-cycle progression during terminal differentiation, which offers insight into the frequent mutation of SWI/SNF genes in human cancers.
authors.affiliation: Developmental Biology, Department of Biology, Faculty of Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Ruijtenberg
authors.affiliation: Developmental Biology, Department of Biology, Faculty of Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: s.j.l.vandenheuvel@uu.nl.
authors.forename: Sander
authors.initials: S
authors.lastname: van den Heuvel
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C066645:HLH-1 protein, C elegans