CNRS/INSERM U964, Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, France;
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Genes Dev. 2014 May 15;28(10):1042-7. doi: 10.1101/gad.238881.114.
The fusion of the gametes upon fertilization results in the formation of a totipotent cell. Embryonic chromatin is expected to be able to support a large degree of plasticity. However, whether this plasticity relies on a particular conformation of the embryonic chromatin is unknown. Moreover, whether chromatin plasticity is functionally linked to cellular potency has not been addressed. Here, we adapted fluorescence recovery after photobleaching (FRAP) in the developing mouse embryo and show that mobility of the core histones H2A, H3.1, and H3.2 is unusually high in two-cell stage embryos and decreases as development proceeds. The transition toward pluripotency is accompanied by a decrease in histone mobility, and, upon lineage allocation, pluripotent cells retain higher mobility than the differentiated trophectoderm. Importantly, totipotent two-cell-like embryonic stem cells also display high core histone mobility, implying that reprogramming toward totipotency entails changes in chromatin mobility. Our data suggest that changes in chromatin dynamics underlie the transitions in cellular plasticity and that higher chromatin mobility is at the nuclear foundations of totipotency.
精卵融合受精导致全能细胞的形成。胚胎染色质有望能够支持很大程度的可塑性。然而，这种可塑性是否依赖于胚胎染色质的特定构象尚不清楚。此外，染色质可塑性是否与细胞潜能功能相关尚未得到解决。在这里，我们在发育中的小鼠胚胎中适应了光漂白后荧光恢复（FRAP），并表明核心组蛋白 H2A、H3.1 和 H3.2 的流动性在两细胞期胚胎中异常高，并随着发育的进行而降低。向多能性的转变伴随着组蛋白流动性的降低，并且在谱系分配后，多潜能细胞保留比分化的滋养外胚层更高的流动性。重要的是，全能的两细胞样胚胎干细胞也表现出高核心组蛋白流动性，这意味着向全能性的重编程需要染色质流动性的改变。我们的数据表明，染色质动力学的变化是细胞可塑性转变的基础，并且更高的染色质流动性是全能性的核基础。
