Genomic regulatory regions: Insights from comparative sequence analysis

Current Opinion in Genetics and Development

Volumn 13, Issue 6, 2003, Pages 604-610

  Cooper, Gregory M ^a   Sidow, Arend ^a,b  

^a STANFORD UNIVERSITY   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGY; CHICKEN; CHROMATIN; CLADISTICS; COMPARATIVE STUDY; DNA TRANSCRIPTION; DROSOPHILA; ENHANCER REGION; FROG; GENE CONTROL; GENE EXPRESSION; GENE SEQUENCE; GENOME; HUMAN; INVERTEBRATE; MAMMAL; NONHUMAN; PHYLOGENY; PRIORITY JOURNAL; PROMOTER REGION; PUFFER FISH; REVIEW; SEQUENCE ANALYSIS; SILENCER GENE; SPECIES DIFFERENCE; SPECIES DIFFERENTIATION; VERTEBRATE; YEAST; ZEBRA FISH;

ANURA; DANIO RERIO; GALLUS GALLUS; INVERTEBRATA; MAMMALIA; TETRAODONTIDAE; VERTEBRATA;

EID: 0344153727     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2003.10.001     Document Type: Review

References (46)

1. Collins F.S., Green E.D., Guttmacher A.E., Guyer M.S. A vision for the future of genomics research. Nature. 422:2003;835-847 This paper provides a perspective on the future of genomics research, including goals for research, and comments on the methodology necessary to achieve those goals. The importance of the identification and characterization of all human functional elements, including regulatory elements, is discussed.
2. Waterston R.H., Lindblad-Toh K., Birney E., Rogers J., Abril J.F., Agarwal P., Agarwal R., Ainscough R., Alexandersson M., An P.et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 420:2002;520-562.
3. Hardison R.C. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet. 16:2000;369-372.
4. Sidow A. Sequence first. Ask questions later. Cell. 111:2002;13-16.
5. Eddy S.R. Computational genomics of noncoding RNA genes. Cell. 109:2002;137-140.
6. Trinklein N.D., Aldred S.J., Saldanha A.J., Myers R.M. Identification and functional analysis of human transcriptional promoters. Genome Res. 13:2003;308-312 The authors predict the promoters of ~10,000 human genes. They test a random selection of 152 of these predictions, confirming that 89% are capable of promoting expression in a cell-culture luciferase reporter assay for at least two types of cell. These cell types may not reflect the genes' native expression domains. This suggests that promoters may function promiscuously in general, and that other factors are necessary for precise spatiotemporal control of gene expression.
7. Di Gregorio A., Corbo J.C., Levine M. The regulation of forkhead/HNF-3β expression in the Ciona embryo. Dev Biol. 229:2001;31-43.
8. Dehal P., Satou Y., Campbell R.K., Chapman J., Degnan B., De Tomaso A., Davidson B., Di Gregorio A., Gelpke M., Goodstein D.M.et al. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science. 298:2002;2157-2167.
9. Keys D.N., Levine M., Harland R.M., Wallingford J.B. Control of intercalation is cell-autonomous in the notochord of Ciona intestinalis. Dev Biol. 246:2002;329-340.
10. Satoh N. The ascidian tadpole larva: comparative molecular development and genomics. Nat Rev Genet. 4:2003;285-295.
11. Harafuji N., Keys D.N., Levine M. Genome-wide identification of tissue-specific enhancers in the Ciona tadpole. Proc Natl Acad Sci USA. 99:2002;6802-6805 Random genomic fragments from Ciona, ~2 kb in size, are generated and tested for their ability to direct tissue-specific expression in Ciona larvae. Eleven fragments produce localized expression, and at least five authentic enhancers are identified, suggesting an enhancer density of 1 per 20-50 kb of genomic DNA. The results may provide the basis for much larger future screens.
12. Ogbourne S., Antalis T.M. Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes. Biochem J. 331:1998;1-14.
13. Donda A., Schulz M., Burki K., De Libero G., Uematsu Y. Identification and characterization of a human CD4 silencer. Eur J Immunol. 26:1996;493-500.
14. Koskinen R., Salomonsen J., Tregaskes C.A., Young J.R., Goodchild M., Bumstead N., Vainio O. The chicken CD4 gene has remained conserved in evolution. Immunogenetics. 54:2002;520-525 The authors sequence the CD4 gene in chicken and report that the gene is conserved between mammals and chicken. In addition, a functional human silencer [13] also seems to be conserved in chicken.
15. Burgess-Beusse B., Farrell C., Gaszner M., Litt M., Mutskov V., Recillas-Targa F., Simpson M., West A., Felsenfeld G. The insulation of genes from external enhancers and silencing chromatin. Proc Natl Acad Sci USA. 99(Suppl 4):2002;16433-16437.
16. West A.G., Gaszner M., Felsenfeld G. Insulators: many functions, many mechanisms. Genes Dev. 16:2002;271-288.
17. Kmita M., Tarchini B., Duboule D., Herault Y. Evolutionary conserved sequences are required for the insulation of the vertebrate Hoxd complex in neural cells. Development. 129:2002;5521-5528 Hox genes play crucial roles in controlling vertebrate morphology, and their expression is precisely regulated in developing vertebrate organisms. Genomic organization of Hox genes as clusters, with a specific ordering of genes within the clusters, is important for achieving this precise regulation. The authors discover genomic sequences that are necessary for insulating the Hoxd cluster from external influences, including one genomic element that is conserved among mouse, chicken and zebrafish.
18. Farrell C.M., West A.G., Felsenfeld G. Conserved CTCF insulator elements flank the mouse and human β-globin loci. Mol Cell Biol. 22:2002;3820-3831 The authors report the discovery of conserved genomic regions that flank the β-globin loci in human and mouse. These regions contain binding sites for CTCF, a protein known to be important for enhancer-blocking insulator activity, and are capable of blocking enhancer activity in vitro.
19. Cremer T., Cremer C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet. 2:2001;292-301.
20. Glazko G.V., Koonin E.V., Rogozin I.B., Shabalina S.A. A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions. Trends Genet. 19:2003;119-124 The authors use a previous study [46] in which large stretches of intergenic sequence were aligned between human and mouse and strongly conserved segments were identified. They correlate those segments with MARs, which are predicted by programs that scan for sequence motifs indicative of MARs. The authors conclude that as much as 11% of the strongly conserved segments consist of MARs; they also note that many of the conserved MARs precede the 5′ ends of genes, which may be a consequence of a role in regulating transcription.
21. Martin D.I. Transcriptional enhancers - on/off gene regulation as an adaptation to silencing in higher eukaryotic nuclei. Trends Genet. 17:2001;444-448.
22. Davidson EH: Genomic Regulatory Systems: Development and Evolution. San Diego, CA: Academic Press; 2001.
23. Kimura M: The Neutral Theory of Molecular Evolution. Cambridge, UK: Cambridge University Press; 1983.
24. Sumiyama K., Kim C.B., Ruddle F.H. An efficient cis-element discovery method using multiple sequence comparisons based on evolutionary relationships. Genomics. 71:2001;260-262.
25. Cooper G.M., Brudno M., Program N.C., Green E.D., Batzoglou S., Sidow A. Quantitative estimates of sequence divergence for comparative analyses of mammalian genomes. Genome Res. 13:2003;813-820.
26. Kellis M., Patterson N., Endrizzi M., Birren B., Lander E.S. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature. 423:2003;241-254 The authors perform a thorough analysis on alignments among four species of yeast, generating precise estimates of Saccharomyces open reading frames and discovering many putative regulatory elements. Furthermore, they use informatic approaches to find shared sequence motifs in conserved noncoding regions and use these to generate hypotheses regarding gene networks and combinatorial control of gene expression.
27. Lim L.P., Glasner M.E., Yekta S., Burge C.B., Bartel D.P. Vertebrate microRNA genes. Science. 299:2003;1540 Using a model to discover microRNAs on the basis of comparative sequence analysis between C. elegans and C. briggsae, the authors are able to generate predictions for the presence of microRNAs in the human, mouse and Fugu genomes. Between 200 and 255 such microRNAs are predicted to exist in the human genome.
28. Wittkopp P.J., Vaccaro K., Carroll S.B. Evolution of yellow gene regulation and pigmentation in Drosophila. Curr Biol. 12:2002;1547-1556 An excellent example of the power of Drosophila cross-species analysis, this paper analyzes genomic changes that may underlie the divergence of pigmentation pattern among drosophilids. The authors suggest that both coding and noncoding changes are likely to have had roles in this phenotypic divergence.
29. Aparicio S., Chapman J., Stupka E., Putnam N., Chia J.M., Dehal P., Christoffels A., Rash S., Hoon S., Smit A.et al. Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science. 297:2002;1301-1310.
30. Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W.et al. Initial sequencing and analysis of the human genome. Nature. 409:2001;860-921.
31. Göttgens B., Barton L.M., Chapman M.A., Sinclair A.M., Knudsen B., Grafham D., Gilbert J.G., Rogers J., Bentley D.R., Green A.R. Transcriptional regulation of the stem cell leukemia gene (SCL) - comparative analysis of five vertebrate SCL loci. Genome Res. 12:2002;749-759 SCL is an important gene involved in vertebrate hematopoiesis. The authors report the characterization of the zebrafish SCL locus, and compare it to the Fugu, chicken, human and mouse sequences. A regulatory region is found to contain several conserved motifs that are essential for regulating SCL expression in hematopoietic cells.
32. Ghanem N., Jarinova O., Amores A., Long Q., Hatch G., Park B.K., Rubenstein J.L., Ekker M. Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters. Genome Res. 13:2003;533-543 Genomic elements that are conserved between fish and mammalian species near the Dlx bigene clusters are discovered. Moreover, they are functionally characterized as enhancers that are capable of directing expression to the forebrain. This result may shed light on the genomic changes that accompanies the acquisition of vertebrate characteristics.
33. Depew M.J., Lufkin T., Rubenstein J.L. Specification of jaw subdivisions by Dlx genes. Science. 298:2002;381-385.
34. Spitz F., Gonzalez F., Duboule D. A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell. 113:2003;405-417 The authors report the discovery of a cluster of enhancer elements that are conserved between mammals and Fugu. This cluster is capable of coordinating expression between Hoxd genes and nearby genes that are evolutionarily unrelated. This includes a newly identified gene that the authors name lunapark.
35. Uchikawa M., Ishida Y., Takemoto T., Kamachi Y., Kondoh H. Functional analysis of chicken Sox2 enhancers highlights an array of diverse regulatory elements that are conserved in mammals. Dev Cell. 4:2003;509-519 Several enhancers of Sox2, a gene involved in the specification of neural cell identities, are functionally detected in chickens. These enhancers correspond precisely to blocks of strong sequence conservation among human, mouse and chicken.
36. Brudno M., Do C.B., Cooper G.M., Kim M.F., Davydov E., Green E.D., Sidow A., Batzoglou S. LAGAN and Multi-LAGAN: efficient tools for large-scale multiple alignment of genomic DNA. Genome Res. 13:2003;721-731.
37. Loots G.G., Locksley R.M., Blankespoor C.M., Wang Z.E., Miller W., Rubin E.M., Frazer K.A. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science. 288:2000;136-140.
38. Qiu Y., Cavelier L., Chiu S., Yang X., Rubin E., Cheng J.F. Human and mouse ABCA1 comparative sequencing and transgenesis studies revealing novel regulatory sequences. Genomics. 73:2001;66-76.
39. Dermitzakis E.T., Reymond A., Lyle R., Scamuffa N., Ucla C., Deutsch S., Stevenson B.J., Flegel V., Bucher P., Jongeneel C.V.et al. Numerous potentially functional but non-genic conserved sequences on human chromosome 21. Nature. 420:2002;578-582 This comparison between human and mouse sequence detects a large amount of noncoding conserved sequence. In addition, a thorough analysis is performed to ensure that these conserved blocks are neither protein coding nor RNA coding, confirming the presence of many important regulatory elements distributed throughout the mammalian genome.
40. Kondrashov A.S., Shabalina S.A. Classification of common conserved sequences in mammalian intergenic regions. Hum Mol Genet. 11:2002;669-674.
41. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Miklos G.L., Wides R., Halpern A., Li P.W., Sutton G.G., Nadeau J.et al. A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome. Science. 296:2002;1661-1671.
42. Carroll S.B. Genetics and the making of Homo sapiens. Nature. 422:2003;849-857.
43. Boffelli D., McAuliffe J., Ovcharenko D., Lewis K.D., Ovcharenko I., Pachter L., Rubin E.M. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science. 299:2003;1391-1394 Comparisons of many primate sequences can and will yield exciting insights into the functional elements that are important to distinguish humans and their closest relatives from other mammals. This paper represents a striking example of this.
44. Ackerman H., Udalova I., Hull J., Kwiatkowski D. Evolution of a polymorphic regulatory element in interferon-γ through transposition and mutation. Mol Biol Evol. 19:2002;884-890.
45. Prokunina L., Castillejo-Lopez C., Oberg F., Gunnarsson I., Berg L., Magnusson V., Brookes A.J., Tentler D., Kristjansdottir H., Grondal G.et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 32:2002;666-669 Relatively few mutations in regulatory DNA (other than in splice sites) that are responsible for human genetic diseases have been reported; this paper is one such example.
46. Shabalina S.A., Ogurtsov A.Y., Kondrashov V.A., Kondrashov A.S. Selective constraint in intergenic regions of human and mouse genomes. Trends Genet. 17:2001;373-376.