Epigenetic mechanisms, including histone modifications, are likely to play crucial roles in the cell-fate maintenance. Recently, we found that the C. elegans acetylated-histone-binding protein BET-1 and MYST family histone acetyltransferases (MYST HATs) are required for the maintenance of cell fates in various cell lineages, indicating that histone acetylation plays a crucial role in the cell-fate maintenance. BET-1 prevents the ectopic expressions of cell-type-specific genes, such as
mec-3, suggesting that BET-1 and MYST HATs maintain the transcriptional repression.
To further elucidate the mechanism to maintain cell fates, we screened genes that phenocopy, enhance and suppress the
bet-1 mutant phenotype by RNAi. RNAi screening revealed that
bet-1 phenotype was phenocopied by RNAi of
ssl-1 and
ekl-4 that are required for the deposition of histone H2A variant, H2A.z/HTZ-1. We also found that the disruption of
htz-1 enhanced the phenotype of a weak
bet-1 allele, but not that of a null allele, indicating
htz-1 and
bet-1 functions in the same genetic pathway for the maintenance of cell fates. One of the suppressors was UTX-1 that demethylates a silencing mark, methylation on H3K27.
utx-1 RNAi suppressed the defect of the cell-fate maintenance in multiple lineages of
bet-1 mutants. These genetic interactions suggest that histone acetylation, methylation and H2A.z cooperate to maintain the stable cell-fates. We speculate that, when UTX-1 removes the silencing mark, H3K27Me, BET-1 and HTZ-1 maintains the transcriptional repression of cell-type-specific genes.