Transcriptional regulation constrains the organization of genes on eukaryotic chromosomes

被引:52
作者
Janga, Sarath Chandra [1 ]
Collado-Vides, Julio [2 ]
Babu, M. Madan [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
[2] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Programa Genom Computac, Mexico City 62100, DF, Mexico
基金
英国医学研究理事会;
关键词
gene order; genome; nuclear architecture; systems biology; network;
D O I
10.1073/pnas.0806317105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Genetic material in eukaryotes is tightly packaged in a hierarchical manner into multiple linear chromosomes within the nucleus. Although it is known that eukaryotic transcriptional regulation is complex and requires an intricate coordination of several molecular events both in space and time, whether the complexity of this process constrains genome organization is still unknown. Here, we present evidence for the existence of a higher-order organization of genes across and within chromosomes that is constrained by transcriptional regulation. In particular, we reveal that the target genes (TGs) of transcription factors (TFs) for the yeast, Saccharomyces cerevisiae, are encoded in a highly ordered manner both across and within the 16 chromosomes. We show that (i) the TGs of a majority of TFs show a strong preference to be encoded on specific chromosomes, (ii) the TGs of a significant number of TFs display a strong preference (or avoidance) to be encoded in regions containing particular chromosomal landmarks such as telomeres and centromeres, and (iii) the TGs of most TFs are positionally clustered within a chromosome. Our results demonstrate that specific organization of genes that allowed for efficient control of transcription within the nuclear space has been selected during evolution. We anticipate that uncovering such higher-order organization of genes in other eukaryotes will provide insights into nuclear architecture, and will have implications in genetic engineering experiments, gene therapy, and understanding disease conditions that involve chromosomal aberrations.
引用
收藏
页码:15761 / 15766
页数:6
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