Sat, 26 Jul 2008 06:23:49 BST CiteULike: emptyhb's Rubin http://www.citeulike.org/user/emptyhb/author/Rubin CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/emptyhb/article/1206695 <i>Nat Rev Genet, Vol. 5, No. 6. (June 2004), pp. 456-465.</i> Comparative genomics at the vertebrate extremes. D Boffelli MA Nobrega EM Rubin doi:10.1038/nrg1350 Nat Rev Genet, Vol. 5, No. 6. (June 2004), pp. 456-465. 2007-04-04T20:07:25-00:00 2004 Nat Rev Genet 1471-0056 5 6 456 465 cis_regulatory_elements cis_regulatory_evolution review http://www.citeulike.org/user/emptyhb/article/698675 <i>Genome Res (12 June 2006)</i><br /><br />Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons. To address this problem, we identified evolutionarily conserved noncoding regions in primate, mammalian, and more distant comparisons using a uniform approach (Gumby) that facilitates unbiased assessment of the impact of evolutionary distance on predictive power. We benchmarked computational predictions against previously identified cis-regulatory elements at diverse genomic loci and also tested numerous extremely conserved human-rodent sequences for transcriptional enhancer activity using an in vivo enhancer assay in transgenic mice. Human regulatory elements were identified with acceptable sensitivity (53%-80%) and true-positive rate (27%-67%) by comparison with one to five other eutherian mammals or six other simian primates. More distant comparisons (marsupial, avian, amphibian, and fish) failed to identify many of the empirically defined functional noncoding elements. Our results highlight the practical utility of close sequence comparisons, and the loss of sensitivity entailed by more distant comparisons. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole-genome comparative analysis that explains most of the observations from empirical benchmarking. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for in vivo testing at embryonic time points. Close sequence comparisons are sufficient to identify human cis-regulatory elements. Shyam Prabhakar Francis Poulin Malak Shoukry Veena Afzal Edward M Rubin Olivier Couronne Len A Pennacchio doi:10.1101/gr.4717506 Genome Res (12 June 2006) 2006-06-16T19:46:25-00:00 2006 Genome Res 1088-9051 cis_regulatory_elements cis_regulatory_evolution motif_searching http://www.citeulike.org/user/emptyhb/article/2211514 <i>Nat Genet (6 January 2008)</i><br /><br />Extended perfect human-rodent sequence identity of at least 200 base pairs (ultraconservation) is potentially indicative of evolutionary or functional uniqueness. We used a transgenic mouse assay to compare the embryonic enhancer activity of 231 noncoding ultraconserved human genome regions with that of 206 extremely conserved regions lacking ultraconservation. Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Axel Visel Shyam Prabhakar Jennifer A Akiyama Malak Shoukry Keith D Lewis Amy Holt Ingrid Plajzer-Frick Veena Afzal Edward M Rubin Len A Pennacchio doi:10.1038/ng.2007.55 Nat Genet (6 January 2008) 2008-01-09T17:38:56-00:00 2008 Nat Genet 1546-1718 cis_regulatory_elements http://www.citeulike.org/user/emptyhb/article/1666879 <i>Proc Natl Acad Sci U S A, Vol. 99, No. 2. (22 January 2002), pp. 757-762.</i><br /><br />A major challenge in interpreting genome sequences is understanding how the genome encodes the information that specifies when and where a gene will be expressed. The first step in this process is the identification of regions of the genome that contain regulatory information. In higher eukaryotes, this cis-regulatory information is organized into modular units [cis-regulatory modules (CRMs)] of a few hundred base pairs. A common feature of these cis-regulatory modules is the presence of multiple binding sites for multiple transcription factors. Here, we evaluate the extent to which the tendency for transcription factor binding sites to be clustered can be used as the basis for the computational identification of cis-regulatory modules. By using published DNA binding specificity data for five transcription factors active in the early Drosophila embryo, we identified genomic regions containing unusually high concentrations of predicted binding sites for these factors. A significant fraction of these binding site clusters overlap known CRMs that are regulated by these factors. In addition, many of the remaining clusters are adjacent to genes expressed in a pattern characteristic of genes regulated by these factors. We tested one of the newly identified clusters, mapping upstream of the gap gene giant (gt), and show that it acts as an enhancer that recapitulates the posterior expression pattern of gt. Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome. BP Berman Y Nibu BD Pfeiffer P Tomancak SE Celniker M Levine GM Rubin MB Eisen doi:10.1073/pnas.231608898 Proc Natl Acad Sci U S A, Vol. 99, No. 2. (22 January 2002), pp. 757-762. 2007-09-17T19:14:17-00:00 2002 Proc Natl Acad Sci U S A 0027-8424 99 2 757 762 cis_regulatory_elements motif_searching http://www.citeulike.org/user/emptyhb/article/2031739 <i>Science, Vol. 318, No. 5855. (30 November 2007), pp. 1449-1452.</i><br /><br />Horizontal gene transfer, in which genetic material is transferred from the genome of one organism to that of another, has been investigated in microbial species mainly through computational sequence analyses. To address the lack of experimental data, we studied the attempted movement of 246,045 genes from 79 prokaryotic genomes into Escherichia coli and identified genes that consistently fail to transfer. We studied the mechanisms underlying transfer inhibition by placing coding regions from different species under the control of inducible promoters. Our data suggest that toxicity to the host inhibited transfer regardless of the species of origin and that increased gene dosage and associated increased expression may be a predominant cause for transfer failure. Although these experimental studies examined transfer solely into E. coli, a computational analysis of gene-transfer rates across available bacterial and archaeal genomes supports that the barriers observed in our study are general across the tree of life. 10.1126/science.1147112 Genome-Wide Experimental Determination of Barriers to Horizontal Gene Transfer Rotem Sorek Yiwen Zhu Christopher Creevey Pilar Francino Peer Bork Edward Rubin doi:10.1126/science.1147112 Science, Vol. 318, No. 5855. (30 November 2007), pp. 1449-1452. 2007-11-30T19:08:53-00:00 2007 Science 318 5855 1449 1452 horizontal_gene_transfer prokaryote