Komoto Tetsushi, Fujii Masashi, Awazu Akinori
Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526, Japan.
Research Center for the Mathematics on Chromatin Live Dynamics, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526, Japan.
Biophys Physicobiol. 2022 May 10;19:1-14. doi: 10.2142/biophysico.bppb-v19.0018. eCollection 2022.
X chromosome inactivation center (Xic) pairing occurs during the differentiation of embryonic stem (ES) cells from female mouse embryos, and is related to X chromosome inactivation, the circadian clock, intra-nucleus architecture, and metabolism. However, the mechanisms underlying the identification and approach of X chromosome pairs in the crowded nucleus are unclear. To elucidate the driving force of Xic pairing, we developed a coarse-grained molecular dynamics model of intranuclear chromosomes in ES cells and in cells 2 days after the onset of differentiation (2-day cells) by considering intrachromosomal epigenetic-structural feature-dependent mechanics. The analysis of the experimental data showed that X-chromosomes exhibit the rearrangement of their distributions of open/closed chromatin regions on their surfaces during cell differentiation. By simulating models where the excluded volume effects of closed chromatin regions are stronger than those of open chromatin regions, such rearrangement of open/closed chromatin regions on X-chromosome surfaces promoted the mutual approach of the Xic pair. These findings suggested that local intrachromosomal epigenetic features may contribute to the regulation of cell species-dependent differences in intranuclear architecture.
X染色体失活中心（Xic）配对发生在雌性小鼠胚胎的胚胎干细胞分化过程中，并且与X染色体失活、生物钟、核内结构和代谢相关。然而，在拥挤的细胞核中识别和靠近X染色体对的潜在机制尚不清楚。为了阐明Xic配对的驱动力，我们通过考虑染色体内表观遗传结构特征依赖性力学，建立了胚胎干细胞和分化开始2天后的细胞（2天龄细胞）内核内染色体的粗粒度分子动力学模型。对实验数据的分析表明，在细胞分化过程中，X染色体表面开放/封闭染色质区域的分布会发生重排。通过模拟封闭染色质区域的排除体积效应强于开放染色质区域的模型，X染色体表面开放/封闭染色质区域的这种重排促进了Xic对的相互靠近。这些发现表明，局部染色体内表观遗传特征可能有助于调节核内结构中细胞类型依赖性差异。
