PDF(Pubmed)
Abstract：
Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionally trans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes in components of gene regulatory complexes.In summary, this study demonstrates the existence of trans-acting effects and compensation mechanisms in human aneuploidies and contributes to our understanding of gene expression regulation in unbalanced genomes and disease states.
摘要：
非整倍性的基因组失衡通常对生物体有害。为了深入了解人类非整倍体的分子基础，我们分析了几种常染色体和性染色体非整倍体的转录组数据.结果表明,在人类非整倍体细胞中,位于不变染色体上的基因是反向或按比例反式调节的，而不同染色体上的基因子集被补偿。由于X失活和在两个性染色体上保留剂量敏感调节剂以限制有效剂量变化，与常染色体非整倍性相比，发现性染色体非整倍性的全基因组调节较少。我们还发现lncRNA和mRNA对非整倍性有不同的反应。此外，我们分析了剂量敏感转录因子与其靶标之间的关系，这说明了调制，并表明基因组失衡与基因调控复合物成分的化学计量变化有关。总之,这项研究证明了在人类非整倍体中存在反式作用和补偿机制,并有助于我们理解不平衡基因组和疾病状态中的基因表达调控.
