coordinated expression domains in mammalian genomes协调在哺乳动物基因组表达域.pdfVIP

Coordinated Expression Domains in Mammalian Genomes ¤ Yong H. Woo , Michael Walker, Gary A. Churchill* The Jackson Laboratory, Center for Genome Dynamics, Bar Harbor, Maine, United States of America Abstract Background: 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. Citation: Woo YH, Walker M, Churchill GA (2010) Coordinated Expression Domains in Mammalian Genomes. PLoS ONE 5(8): e12158. doi:10.1371/ journal.pone.0012158 Editor: Vladimir Brusic, Dana-Farber Cancer Institute, United States of America Received April