Mitosis gives a brief window of opportunity for a change in gene transcription.

Abstract

Author SummaryCells are dividing very actively at a time in development when new gene expression and new cell lineages arise. At mitosis, most transcription factors are temporarily displaced from chromosomes. We show that, after transplantation to oocytes, somatic cell nuclei that have been synchronized in mitosis can be reprogrammed to pluripotency gene expression up to 100 times faster than interphase nuclei. We find that, as cells traverse mitosis, their genes pass through a temporary phase of unusually high responsiveness to oocyte reprogramming factors (mitotic advantage). Many other genes in the genome have also shown a mitotic advantage, which affects the rate rather than the final level of transcriptional enhancement. This is attributable to a chromatin state rather than to more rapid passage of reprogramming factors through the nuclear membrane. Histone H2A deubiquitination at mitosis is required for the acquisition of mitotic advantage. Our results support the general principle that a temporary access of cytoplasmic factors to genes during mitosis facilitates somatic cell nuclear reprogramming and the acquisition of new cell fates in normal development.