title: Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C. elegans.
abstract: The maintenance of cell fate is important for normal development and tissue homeostasis. Epigenetic mechanisms, including histone modifications, are likely to play crucial roles in cell-fate maintenance. However, in contrast to the established functions of histone methylation, which are mediated by the polycomb proteins, the roles of histone acetylation in cell-fate maintenance are poorly understood. Here, we show that the C. elegans acetylated-histone-binding protein BET-1 is required for the establishment and maintenance of stable fate in various lineages. In most bet-1 mutants, cells adopted the correct fate initially, but at later stages they often transformed into a different cell type. By expressing BET-1 at various times in development and examining the rescue of the Bet-1 phenotype, we showed that BET-1 functions both at the time of fate acquisition, to establish a stable fate, and at later stages, to maintain the established fate. Furthermore, the disruption of the MYST HATs perturbed the subnuclear localization of BET-1 and caused bet-1-like phenotypes, suggesting that BET-1 is recruited to its targets through acetylated histones. Our results therefore indicate that histone acetylation plays a crucial role in cell-fate maintenance.
authors.affiliation: Laboratory for Cell Fate Decision, Riken, Center for Developmental Biology, Kobe, Hyogo, 650-0047, Japan.
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Shibata
authors.forename: Hisako
authors.initials: H
authors.lastname: Takeshita
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasakawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sawa
mesh_terms: D000107:Acetylation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D019070:Cell Lineage; D002875:Chromosomes / Q000378:metabolism; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D009030:Mosaicism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C548500:BET-1 protein, C elegans; D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D006657:Histones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D051548:Histone Acetyltransferases