Display Settings:

Format

Send to:

Choose Destination
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15761-6. doi: 10.1073/pnas.0806317105. Epub 2008 Oct 7.

Transcriptional regulation constrains the organization of genes on eukaryotic chromosomes.

Author information

  • 1Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 0QH, United Kingdom. sarath@mrc-lmb.cam.ac.uk

Abstract

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.

PMID:
18840678
[PubMed - indexed for MEDLINE]
PMCID:
PMC2562535
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk