Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C. elegans.
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.
Shibata
Yukimasa
Y
Laboratory for Cell Fate Decision, Riken, Center for Developmental Biology, Kobe, Hyogo, 650-0047, Japan.
Takeshita
Hisako
H
Sasakawa
Noriko
N
Sawa
Hitoshi
H
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
C548500:BET-1 protein, C elegans; D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D006657:Histones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D051548:Histone Acetyltransferases