In general, differentiation is the irreversible step that loose the potential to produce certain cell-types, although artificial transdifferentiation or induction of iPS cells overcomes the loss of developmental potential. We previously reported that histone H2A variant HTZ-1/H2A.z and acetylated histone H4 binding protein BET-1 prevent transdifferentiation in multiple cell lineages in normal development. Here, we report that, in addition to H2A variant, the balance between two histone H3 variants is also important for the maintenance of differentiation states. We screened mutants with extra-DTCs phenotype that is caused by abnormal transdifferentiation of somatic gonadal cells, as shown in
bet-1 mutants. We isolated
tlk-1 mutants that showed severer phenotype in adulthood than in larvae. It is consistent with abnormal transdifferentiation during the development. In addition to somatic gonadal lineage,
tlk-1 is required in multiple cell lineages, including the Q and V5.pa lineages, indicating that TLK-1 functions as one of the fundamental factors that maintains differentiation states.
tlk-1 encodes a homolog of Tousled like kinase that phosphorylate histone chaperone ASF. It is known that ASF is upstream of histone chaperone CAF1 that mediates replication-coupled nucleosome assembly by deposition of histone H3.1. We found that CAF1 deficient mutant,
chaf-1, is phenocopy of
tlk-1 mutants in the somatic gonadal, Q, and V5.pa lineage. Interestingly, the levels of histone H3 variant, H3.3, were higher in the nuclei of
tlk-1 and
chaf-1 mutants compared to the wild type, suggesting that H3.3 is deposited instead of H3.1. Since H3.3 correlates with open chromatin,
tlk-1 appears to maintain gene silencing through balancing between histones H3.1 and H3.3. Phenotype of
tlk-1 mutant indicated that DNA-binding transcription factors that induce specific cell type are regulated by TLK-1. For example, extra-DTCs in
tlk-1 mutants showed multiple DTC-specific characters. Since
tlk-1 mutants have extra-AVMs, we examined
mec-3 expression and found that ectopic
mec-3 expression occurred. All together, TLK-1 maintains differentiation state through silencing of genes that encodes DNA-binding transcription factors through regulation of histone H3 deposition. Since CAF1 prevents transdifferentiation and induction of iPS in mammals, our results raise the possibility that the transdifferentiation inhibitory mechanism involving TLK-1 and CAF1 is evolutionarily conserved.