PDF(Pubmed)
Abstract：
Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization.
摘要：
三体性是整个染色体或其部分在细胞核中的一个额外拷贝的存在。在人类中,常染色体三体与导致胚胎致死的严重发育异常有关，出生时各种器官和系统的流产或明显偏差。三体的特征是基因表达水平的改变，不仅仅是在三体染色体上，而是整个基因组。这里,我们应用高通量染色体构象捕获技术(Hi-C)研究了携带额外13号染色体(Patau综合征)或16号染色体的人绒毛膜细胞和携带额外18号染色体(Edwards综合征)的培养成纤维细胞的染色质3D结构.额外染色体的存在导致小染色体和大染色体之间接触频率的系统变化。分析单个染色体的行为，我们发现,在三体细胞中,有限数量的染色体随机改变其接触模式,并且可能与层相关结构域(LAD)和基因含量相关.对于13和18三体，而不是16三体，染色体上压缩基因座的比例与LAD含量相关。我们还发现，在三体细胞中变得更紧凑的基因组区域富含管家基因，表明这些基因的染色质可及性和转录水平可能降低。这些结果为在染色质空间组织的背景下理解三体中泛基因组转录失调的机制提供了框架。
