Mediators of reprogramming: transcription factors and transitions through mitosis

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Abstract
The genome remains mostly constant during development and ageing. Cells differ in which part of the genome they express. The gene-expression programme is determined by the presence of transcriptional regulators. The cloning of various organisms from different cell types shows that the differentiated state and cellular changes that occur during ageing are reversible. This reversion is referred to as reprogramming. Transcriptional regulators dissociate from the chromatin during cell division. The transcriptional programme, and with it a cellular state, is newly established after every cell division, thereby challenging the old state as well as providing the opportunity to transit to another state. Exposing a genome to a different set of transcriptional regulators can change its gene-expression programme and with it cellular identity. This can be done by ectopic expression of transcription factors, cell fusion or nuclear transfer. Transfer of a somatic cell genome into an unfertilized oocyte or a zygote in mitosis allows the derivation of pluripotent embryonic stem-cell lines from the cloned preimplantation stage embryos. Fusion of a somatic cell with an embryonic stem cell can reprogramme the somatic cell genome to an embryonic state. The ectopic expression of a combination of embryonic stem-cell transcription factors can reprogramme a somatic cell to an embryonic state.