Shankar Ganesh Akshada, Orban Taylor M, Raj Romir, Fatzinger Peter I, Johnson Anna, Riccard Sean M, Zhanaidarov Akhmed, Inaba Mayu, Erceg Jelena
bioRxiv. 2025 Apr 6:2025.04.06.647428. doi: 10.1101/2025.04.06.647428.
Chromosome territories (CTs) are intricately organized and regulated within the nucleus. Despite remarkable advances in our understanding of genome packaging and gene expression, the interplay among CTs, pairing of parental homologous chromosomes, and genome function during development remains elusive. Here, we employ an Oligopaints-based high-resolution imaging approach to examine variable CT organization in single nuclei during the developmental process of zygotic genome activation. We reveal large-scale chromosome changes with extensive homolog pairing at the whole-chromosome level that decreases locally due to spatial variability in chromosome conformations. In the absence of one homolog copy, the dynamics of CT compaction and RNA polymerase II recruitment are supported by transcriptional changes in haploid embryos. Finally, global inhibition of transcription results in decreased CT opening and no significant impact on CT pairing levels. These findings enhance our understanding of parental genome folding and regulation, which may inform strategies for chromosome-based diseases.
染色体领地（CTs）在细胞核内有着复杂的组织和调控。尽管我们对基因组包装和基因表达的理解取得了显著进展，但在发育过程中，CTs之间的相互作用、亲本同源染色体的配对以及基因组功能仍不清楚。在这里，我们采用基于寡核苷酸荧光原位杂交的高分辨率成像方法，来研究合子基因组激活发育过程中单细胞核内可变的CT组织。我们揭示了在全染色体水平上有广泛同源配对的大规模染色体变化，这种变化由于染色体构象的空间变异性而局部减少。在缺少一个同源拷贝的情况下，单倍体胚胎中的转录变化支持了CT压缩和RNA聚合酶II募集的动力学。最后，转录的全局抑制导致CT开放减少，且对CT配对水平没有显著影响。这些发现增进了我们对亲本基因组折叠和调控的理解，这可能为基于染色体的疾病提供策略依据。
