Maintenance of Cell Fates by Regulation of the Histone Variant H3.3 inCaenorhabditis elegans

Highlights TLK-1 maintains cell fates by repression of selector genes TLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 deposition Loss of sin-3 suppresses the defect in cell-fate maintenance of tlk-1 mutants AcH4-binding protein BET-1 is necessary for sin-3 suppression Summary Cell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone H4-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans tousled-like kinase TLK-1 and the histone H3 chaperone CAF1 maintain cell fate by preventing the incorporation of histone variant H3.3 into nucleosomes, thereby repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.