Martin Catherine, Beaujean Nathalie, Brochard Vincent, Audouard Christophe, Zink Daniele, Debey Pascale
UMR 13-1198 Biologie du Développment et Reproduction, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
Dev Biol. 2006 Apr 15;292(2):317-32. doi: 10.1016/j.ydbio.2006.01.009.
Although a growing number of studies investigates functional genome organization in somatic cell nuclei, it is largely unknown how mammalian genome organization is established during embryogenesis. To address this question, we investigated chromo center formation and the peculiar arrangements of chromosome domains in early mouse embryos. At the one-cell stage, we observed characteristic arrangements of chromosomes and chromo center components. Subsequently, starting with the burst of zygotic genome transcription major rearrangements led to the establishment of somatic type chromo centers with a defined spatio-temporal organization. These processes appeared to be completed at the blastocyst stage with the onset of cell differentiation. During the same developmental period, a fraction of pericentric heterochromatin that was late replicating in the first cycle underwent switches in replication timing, spatial organization and epigenetic marks. Cloning experiments revealed that the genome organization typical for more advanced stages was quickly reverted into the one-cell stage-specific form after nuclear transfer, supporting the idea that reprogramming associated genome remodeling in normal and cloned embryos is determined by cytoplasmic factors. Together, the results suggest that distinct but characteristic forms of nuclear genome organization are required for genome reprogramming in early embryos and for proper regulation of differential gene expression patterns at later stages.
尽管越来越多的研究调查了体细胞细胞核中的功能基因组组织，但在很大程度上仍不清楚哺乳动物基因组组织在胚胎发生过程中是如何建立的。为了解决这个问题，我们研究了小鼠早期胚胎中的染色体中心形成和染色体结构域的特殊排列。在单细胞阶段，我们观察到了染色体和染色体中心成分的特征性排列。随后，从合子基因组转录爆发开始，主要的重排导致了具有明确时空组织的体细胞型染色体中心的建立。这些过程似乎在囊胚阶段随着细胞分化的开始而完成。在同一发育时期，在第一个周期中复制较晚的一部分着丝粒周围异染色质在复制时间、空间组织和表观遗传标记方面发生了转换。克隆实验表明，核移植后，更高级阶段典型的基因组组织迅速恢复为单细胞阶段特异性形式，这支持了正常胚胎和克隆胚胎中与重编程相关的基因组重塑由细胞质因子决定的观点。总之，这些结果表明，早期胚胎中的基因组重编程以及后期差异基因表达模式的适当调控需要不同但具有特征性的核基因组组织形式。
