Epigenetic factors influencing resistance to nuclear reprogramming.
Bottom Line: Transcription factors, chromatin modifications, and noncoding RNAs can increase the efficiency of reprogramming.However, the success of nuclear reprogramming is limited by epigenetic mechanisms that stabilise the state of gene expression in somatic cells and thereby resist efficient reprogramming.We see this as a step towards understanding the mechanisms by which nuclear reprogramming takes place.
Affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.Show MeSH
Mentions: As cells differentiate, their chromatin becomes increasingly condensed. Nuclear volume is indicative of the average extent of chromatin condensation. We estimate the volume of a nucleus (inversely related to condensation) in lymphocytes, non-mammalian red blood cells, and sperm, to be three, eight or 100 times respectively, smaller than that of an ES cell. In all nuclear transfer experiments, both in eggs and oocytes, a nuclear volume increase of 10–30-fold accompanies new gene transcripts , chromosomal proteins leave the nucleus and chromosomal protein mobility is increased . Likewise, in heterokaryon experiments, similar changes follow cell fusion [6,7,31]. However, changes in nuclear volumes are not sufficient for gene reactivation because Polycomb-deficient ES cells do not induce pluripotency gene reactivation when fused to human B-lymphocytes but nuclear volume changes remain unperturbed . In Figure 3, we present a hypothetical model of chromosomal changes associated with nuclear reprogramming.
Affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.