E2F regulates FASCIATA1, a chromatin assembly gene whose loss switches on the endocycle and activates gene expression...

Maintenance of genome integrity depends on histone chaperone-mediated chromatin reorganization. DNA replication-associated nucleosome deposition relies on chromatin assembly factor-1 (CAF-1). Depletion of CAF-1 in human cells leads to cell death, whereas in Arabidopsis (Arabidopsis thaliana), where it is involved in heterochromatin compaction and homologous recombination, plants are viable. The mechanism that makes the lack of CAF-1 activity compatible with development is not known. Here, we show that the FASCIATA1 (FAS1) gene, which encodes the CAF-1 large subunit, is a target of E2F transcription factors. Mutational studies demonstrate that one of the two E2F binding sites in its promoter has an activator role, whereas the other has a repressor function. Loss of FAS1 results in reduced type A cyclin-dependent kinase activity, inhibits mitotic progression, and promotes a precocious and systemic switch to the endocycle program. Selective up-regulation of the expression of a subset of genes, including those involved in activation of the G2 DNA damage checkpoint, also occurs upon FAS1 loss. This activation is not the result of a global change in chromatin structure, but depends on selective epigenetic changes in histone acetylation and methylation within a small region in their promoters. This suggests that correct chromatin assembly during the S-phase is required to prevent unscheduled changes in the epigenetic marks of target genes. Interestingly, activation of the endocycle switch as well as introduction of activating histone marks in the same set of G2 checkpoint genes are detected upon treatment of wild-type plants with DNA-damaging treatments. Our results are consistent with a model in which defects in chromatin assembly during the S-phase and DNA damage signaling share part of a pathway, which ultimately leads to mitotic arrest and triggers the endocycle program. Together, this might be a bypass mechanism that makes development compatible with cell division arrest induced by DNA damage stress.