The Jackson Laboratory, Center for Genome Dynamics, Bar Harbor, Maine, United States of America.
PLoS One. 2010 Aug 18;5(8):e12158. doi: 10.1371/journal.pone.0012158.
Gene order in eukaryotic genomes is not random. Genes showing similar expression (coexpression) patterns are often clustered along the genome. The goal of this study is to characterize coexpression clustering in mammalian genomes and to investigate the underlying mechanisms.
METHODOLOGY/PRINCIPAL FINDINGS: We detect clustering of coexpressed genes across multiple scales, from neighboring genes to chromosomal domains that span tens of megabases and, in some cases, entire chromosomes. Coexpression domains may be positively or negatively correlated with other domains, within and between chromosomes. We find that long-range expression domains are associated with gene density, which in turn is related to physical organization of the chromosomes within the nucleus. We show that gene expression changes between healthy and diseased tissue samples occur in a gene density-dependent manner.
CONCLUSIONS/SIGNIFICANCE: We demonstrate that coexpression domains exist across multiple scales. We identify potential mechanisms for short-range as well as long-range coexpression domains. We provide evidence that the three-dimensional architecture of the chromosomes may underlie long-range coexpression domains. Chromosome territory reorganization may play a role in common human diseases such as Alzheimer's disease and psoriasis.
真核基因组中的基因排列并非随机。具有相似表达（共表达）模式的基因通常沿基因组聚集。本研究的目的是描述哺乳动物基因组中的共表达聚类，并探讨其潜在机制。
方法/主要发现：我们在多个尺度上检测到共表达基因的聚类，从相邻基因到跨越数十兆碱基甚至整个染色体的染色体区域。共表达域可能与其他域在染色体内和染色体之间呈正相关或负相关。我们发现，长程表达域与基因密度相关，而基因密度又与细胞核内染色体的物理组织有关。我们表明，健康和患病组织样本之间的基因表达变化以基因密度依赖性的方式发生。
结论/意义：我们证明了共表达域存在于多个尺度上。我们确定了短程和长程共表达域的潜在机制。我们提供的证据表明，染色体的三维结构可能是长程共表达域的基础。染色体区域重组可能在阿尔茨海默病和银屑病等常见人类疾病中发挥作用。
