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 [29], chromosomal proteins leave the nucleus and chromosomal protein mobility is increased [30]. 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 [32]. In Figure 3, we present a hypothetical model of chromosomal changes associated with nuclear reprogramming.
