Fig 10. Proposed effects of Setdb1 depletion on meiotic progression and preimplantation development.

Setdb1 depletion in growing oocytes leads to decreases in H3K9-methyl marks. One consequence is elevated expression of Cdc14b, which leads to Cyclin B1 degradation and inhibition of meiotic resumption. Cdc14b upregulation also contributes to subsequent spindle and chromosomal abnormalities and meiotic arrest at meiosis I. Other consequences of decreases in H3K9 methylation, including derepression of retrotransposons, DNA damage, altered gene expression, and chromatin defects, likely also play important roles in inducing spindle and chromosome defects at meiosis I. The mechanisms by which Setdb1 depletion leads to preimplantation development defects remain to be determined. The consequences of Setdb1 depletion (e.g. H3K9 methylation decreases, altered gene expression, and genomic and chromosomal instability) and/or the lack of maternal Setdb1 itself may affect essential cellular processes during preimplantation development.