Sarath Chandra Janga,1,* Julio Collado-Vides,2 M. Madan Babu,1*
1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
2Programa de Genomica Computacional, Centro de Ciencias Genomicas, Universidad Nacional Autonoma de Mexico, Apdo. Postal 565-A, Av Universidad, Cuernavaca, Morelos, 62100 Mexico, Mexico.
*To whom correspondence should be addressed. Emails: madanm@mrc-lmb.cam.ac.uk, sarath@mrc-lmb.cam.ac.uk
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| Abstract |
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Though it is known that eukaryotic transcriptional regulation requires intricate co-ordination 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 of transcription factors for the yeast, Saccharomyces cerevisiae, are encoded in a highly ordered manner both across and within the sixteen chromosomes. We show that the targets of a majority of the transcription factors are not randomly distributed but display a strong preference to be (i) encoded on specific chromosomes, (ii) encoded in regions (or avoid regions) containing particular chromosomal landmarks such as telomeres and centromeres, and (iii) to be 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 chromosomal territories, their role in cellular differentiation and transformation, and will have implications for understanding disease conditions that involve chromosomal aberrations.
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| Supplementary Material |
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1. Supplementary Material 1: Supplementary figure for the introduction DOC |
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2. Supplementary Material 2: Chromosomal Preference for transcription factors XLS |
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3. Supplementary Material 3: (a) Statistics for Preferred no of TFs regulating a chromosome v/s genes, genome size, gene density of chromosomes and (b) Statistics for chromosomal distribution of loci encoding TFs and global regulatory hubs XLS |
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4. Supplementary Material 4: Regional preference for transcription factors XLS |
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5. Supplementary Material 5: Statistics for distribution of TFs and hubs in the three different regions XLS |
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6. Supplementary Material 6: Target Proximity Index (TPI) distribution analysis after controlling for tandem duplication and bi-directional genes PDF |
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7. Supplementary Material 7: Target Proximity Index (TPI) values for TFs in the real and the filtered network XLS |
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8. Supplementary Material 8: Chromosomal preference for human and mouse TFs DOC |
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