Skip to main content
SpringerLink
Log in

In silico identification of metazoan transcriptional regulatory regions

  • Review Article
  • Published:
Naturwissenschaften Aims and scope Submit manuscript

Abstract

Transcriptional regulation remains one of the most intriguing and challenging subjects in biomedical research. The catalysis of transcription is a clear example of multiple proteins interacting to orchestrate a biological process, offering a starting point for the study of biological systems. Transcriptional regulation is viewed as one of the principal mechanisms governing the spatial and temporal distribution of gene expression, thus the field of transcriptional regulation provides a natural stage for quantitative studies of multiple gene systems. Building on the body of focused experimental studies and new genomics-driven data, computational biologists are making significant strides in accelerating our understanding of the transcriptional regulatory process in metazoan cells. Recent advances in the computational analysis of the interplay between factors have been fueled by well-defined computational methods for the modeling of the binding of individual transcription factors. We present here an overview of advances in the analysis of regulatory systems and the fundamental methods that underlie the recent developments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2a–c.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  • Anderson JD, Widom J (2000) Sequence and position-dependence of the equilibrium accessibility of nucleosomal DNA target sites. J Mol Biol 296(4):979–987

    Article  CAS  PubMed  Google Scholar 

  • Arnone MI, Davidson EH (1997) The hardwiring of development: organization and function of genomic regulatory systems. Development 124(10):1851–1864

    CAS  PubMed  Google Scholar 

  • Bailey TL, Elkan C (1995) Unsupervised learning of multiple motifs in biopolymers using expectation maximization. Machine Learning 21:51–83

    Google Scholar 

  • Benos PV, Bulyk ML, Stormo GD (2002) Additivity in protein-DNA interactions: how good an approximation is it? Nucleic Acids Res 30(20):4442–4451

    Article  CAS  PubMed  Google Scholar 

  • Berman BP, Nibu Y, Pfeiffer BD, Tomancak P, Celniker SE, Levine M, Rubin GM, Eisen MB (2002) Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome. Proc Natl Acad Sci USA 99(2):757–762

    Article  CAS  PubMed  Google Scholar 

  • Bird AP (1987) CpG islands as gene markers in the vertebrate nucleus. Trends Genet 3(12):342–347

    Article  CAS  Google Scholar 

  • Blackwood EM, Kadonaga JT (1998) Going the distance: a current view of enhancer action. Science 281:61–63

    Article  CAS  PubMed  Google Scholar 

  • Blanchette M, Tompa M (2002) Discovery of regulatory elements by a computational method for phylogenetic footprinting. Genome Res 12(5):739–748

    Article  CAS  PubMed  Google Scholar 

  • Blanchette M, Schwikowski B, Tompa M (2000) An exact algorithm to identify motifs in orthologous sequences from multiple species. Proc Int Conf Intell Syst Mol Biol 8:37–45

    CAS  PubMed  Google Scholar 

  • Bode J, Benham C, Knopp A, Mielke C (2000) Transcriptional augmentation: modulation of gene expression by scaffold/matrix-attached regions (S/MAR elements). Crit Rev Eukaryot Gene Expr 10(1):73–90

    CAS  PubMed  Google Scholar 

  • Boutanaev AM, Kalmykova AI, Shevelyov YY, Nurminsky DI (2002) Large clusters of co-expressed genes in the Drosophila genome. Nature 420(6916):666–669

    Article  CAS  PubMed  Google Scholar 

  • Boyle S, Gilchrist S, Bridger JM, Mahy NL, Ellis JA, Bickmore WA (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10(3):211–219

    Google Scholar 

  • Brazma A, Jonassen I, Vilo J, Ukkonen E (1998) Predicting gene regulatory elements in silico on a genomic scale. Genome Res 8(11):1202–1215

    CAS  PubMed  Google Scholar 

  • Bucher P (1990) Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. J Mol Biol 212:563–579

    CAS  PubMed  Google Scholar 

  • Bulyk ML, Johnson PL, Church GM (2002) Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors. Nucleic Acids Res 30(5):1255–1261

    Article  CAS  PubMed  Google Scholar 

  • Bussemaker HJ, Li H, Siggia ED (2000) Building a dictionary for genomes: identification of presumptive regulatory sites by statistical analysis. Proc Natl Acad Sci USA 97(18):10096–10100

    Article  CAS  PubMed  Google Scholar 

  • Caron H, Schaik B van, Mee M van der, Baas F, Riggins G, Sluis P van, Hermus MC, Asperen R van, Boon K, Voute PA, Heisterkamp S, Kampen A van, Versteeg R (2001) The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291(5507):1289–1292

    CAS  PubMed  Google Scholar 

  • Chung I, Bresnick E (1997) Identification of positive and negative regulatory elements of the human cytochrome P4501A2 (CYP1A2) gene. Arch Biochem Biophys 338(2):220–226

    Article  CAS  PubMed  Google Scholar 

  • Claverie JM (2000) From bioinformatics to computational biology. Genome Res 10:1277–1279

    Article  CAS  PubMed  Google Scholar 

  • Cohen BA, Mitra RD, Hughes JD, Church GM (2000) A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat Genet 26(2):183–186

    Article  CAS  PubMed  Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2(4):292–301

    Article  CAS  PubMed  Google Scholar 

  • Cremer T, Kreth G, Koester H, Fink RH, Heintzmann R, Cremer M, Solovei I, Zink D, Cremer C (2000) Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture. Crit Rev Eukaryot Gene Expr 10(2):179–212

    CAS  PubMed  Google Scholar 

  • Crowley EM, Roeder K, Bina M (1997) A statistical model for locating regulatory regions in genomic DNA. J Mol Biol 268(1):8–14

    Article  CAS  PubMed  Google Scholar 

  • Davidson EH (2001) Genomic regulatory systems: development and evolution. Academic Press, San Diego

    Google Scholar 

  • Davuluri RV, Grosse I, Zhang MQ (2001) Computational identification of promoters and first exons in the human genome. Nat Genet 29(4):412–417

    Article  CAS  PubMed  Google Scholar 

  • Dempsey AA, Pabalan N, Tang HC, Liew CC (2001) Organization of human cardiovascular-expressed genes on chromosomes 21 and 22. J Mol Cell Cardiol 33(3):587–591

    Article  CAS  PubMed  Google Scholar 

  • Down TA, Hubbard TJ (2002) Computational detection and location of transcription start sites in mammalian genomic DNA. Genome Res 12(3):458–461

    Article  CAS  PubMed  Google Scholar 

  • Dundr M, Misteli T (2001) Functional architecture in the cell nucleus. Biochem J 356(2):297–310

    Article  CAS  PubMed  Google Scholar 

  • Fickett JW (1996a) Quantitative discrimination of MEF2 sites. Mol Cell Biol 16:437–441

    Google Scholar 

  • Fickett JW (1996b) Coordinate positioning of MEF2 and myogenin binding sites. Gene 172(1):GC19–32

    Article  CAS  PubMed  Google Scholar 

  • Fickett JW, Hatzigeorgiou AG (1997) Eukaryotic promoter recognition. Genome Res 7(9):861–878

    CAS  PubMed  Google Scholar 

  • Fickett JW, Wasserman WW (2000) Discovery and modeling of transcriptional regulatory regions. Curr Opin Biotechnol 11:19–24

    Article  CAS  PubMed  Google Scholar 

  • Fournier B, Gutzwiller S, Dittmar T, Matthias G, Steenbergh P, Matthias P (2001) Estrogen receptor (ER)-α, but not ER-β, mediates regulation of the insulin-like growth factor I gene by antiestrogens. J Biol Chem 276(38):35444–35449

    Article  CAS  PubMed  Google Scholar 

  • Frech K, Danescu-Mayer J, Werner T (1997) A novel method to develop highly specific models for regulatory units detects a new LTR in GenBank which contains a functional promoter. J Mol Biol 270(5):674–687

    Article  CAS  PubMed  Google Scholar 

  • Frisch M, Frech K, Klingenhoff A, Cartharius K, Liebich I, W (2002) In silico prediction of scaffold/matrix attachment regions in large genomic sequences. Genome Res 12(2):349–354

    CAS  PubMed  Google Scholar 

  • Frith MC, Hansen U, Weng Z (2001) Detection of cis-element clusters in higher eukaryotic DNA. Bioinformatics 17(10):878–889

    Article  CAS  PubMed  Google Scholar 

  • Frith MC, Spouge JL, Hansen U, Weng Z (2002) Statistical significance of clusters of motifs represented by position-specific scoring matrices in nucleotide sequences. Nucleic Acids Res 30(14):3214–3224

    Article  CAS  PubMed  Google Scholar 

  • Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196(2):261–282

    PubMed  Google Scholar 

  • Gregori C, Porteu A, Lopez S, Kahn A, Pichard AL (1998) Characterization of the aldolase B intronic enhancer. J Biol Chem 273(39):25237–25243

    Article  CAS  PubMed  Google Scholar 

  • GuhaThakurta D, Stormo GD (2001) Identifying target sites for cooperatively binding factors. Bioinformatics 17(7):608–621

    Article  CAS  PubMed  Google Scholar 

  • Halfon MS, Michelson AM (2002) Exploring genetic regulatory networks in metazoan development methods and models. Physiol Genomics 10(3):131–143

    CAS  PubMed  Google Scholar 

  • Halfon MS, Grad Y, Church GM, Michelson AM (2002) Computation-based discovery of related transcriptional regulatory modules and motifs using an experimentally validated combinatorial model. Genome Res 12(7):1019–1028

    CAS  PubMed  Google Scholar 

  • Hannenhalli S, Levy S (2001) Promoter prediction in the human genome. Bioinformatics 17 [suppl 1]:S90–S96

    Google Scholar 

  • Hannenhalli S, Levy S (2002) Predicting transcription factor synergism. Nucleic Acids Res 30(19):4278–4284

    Article  CAS  PubMed  Google Scholar 

  • Helden J van, Andre B, Collado-Vides J (1998) Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies. J Mol Biol 281(5):827–842

    Article  PubMed  Google Scholar 

  • Iyer VR, Horak CE, Scafe CS, Botstein D, Snyder M, Brown PO (2001) Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409(6819):533–538

    Article  CAS  PubMed  Google Scholar 

  • Jackson DA (1997) Chromatin domains and nuclear compartments: establishing sites of gene expression within eukaryotic nuclei. Mol Biol Rep 24(3):209–220

    Article  CAS  PubMed  Google Scholar 

  • Kadonaga JT (1998) Eukaryotic transcription: an interlaced network of transcription factors and chromatin-modifying machines. Cell 92(3):307–313

    CAS  PubMed  Google Scholar 

  • Kel AE, Kel-Margoulis OV, Farnham PJ, Bartley SM, Wingender E, Zhang MQ (2001) Computer-assisted identification of cell cycle-related genes: new targets for E2F transcription factors. J Mol Biol 309(1):99–120

    Article  CAS  PubMed  Google Scholar 

  • Klingenhoff A, Frech K, Quandt K, Werner T (1999) Functional promoter modules can be detected by formal models independent of overall nucleotide sequence similarity. Bioinformatics 15(3):180–186

    Article  CAS  PubMed  Google Scholar 

  • Kornberg RD, Lorch Y (1999) Twenty-five years of the nucleosome: fundamental particle of the eukaryote chromosome. Cell 98(3):285–294

    CAS  PubMed  Google Scholar 

  • Kraus RJ, Murray EE, Wiley SR, Zink NM, Loritz K, Celembiuk GW, Mertz JE (1996) Experimentally determined weight matrix definitions of the initiator and TBP binding site elements of promoters. Nucleic Acids Res 24:1531–1539

    Google Scholar 

  • Krivan W, Wasserman WW (2001) A predictive model for regulatory sequences directing liver-specific transcription. Genome Res 11(9):1559–1666

    Article  CAS  PubMed  Google Scholar 

  • Kruglyak S, Tang H (2000) Regulation of adjacent yeast genes. Trends Genet 16(3):109–111

    Article  CAS  PubMed  Google Scholar 

  • Lawrence CE, Reilly A (1990) An EM algorithm for the identification and characterization of common sites in unaligned biopolymers sequence. Proteins 7:41–51

    CAS  PubMed  Google Scholar 

  • Lawrence CE, Altschul SF, Boguski MS, Liu JS, Neuwald AF, Wootton JC (1993) Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. Science 262:208–214

    CAS  PubMed  Google Scholar 

  • Lemon B, Tjian R (2000) Orchestrated response: a symphony of transcription factors for gene control. Genes Dev 14(20):2551–2569

    Article  CAS  PubMed  Google Scholar 

  • Lercher MJ, Urrutia AO, Hurst LD (2002) Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 31(2):180–183

    Article  CAS  PubMed  Google Scholar 

  • Levitsky VG, Podkolodnaya OA, Kolchanov NA, Podkolodny NL (2001) Nucleosome formation potential of eukaryotic DNA: calculation and promoters analysis. Bioinformatics 17(11):998–1010

    Article  CAS  PubMed  Google Scholar 

  • Levy S, Hannenhalli S (2002) Identification of transcription factor binding sites in the human genome sequence. Mamm Genome 13(9):510–514

    Article  CAS  PubMed  Google Scholar 

  • Levy S, Hannenhalli S, Workman C (2001) Enrichment of regulatory signals in conserved non-coding genomic sequence. Bioinformatics 17(10):871–877

    Article  CAS  PubMed  Google Scholar 

  • Liu R, States DJ (2002) Consensus promoter identification in the human genome utilizing expressed gene markers and gene modeling. Genome Res 12(3):462–469

    Article  CAS  PubMed  Google Scholar 

  • Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288:136–140

    Article  CAS  PubMed  Google Scholar 

  • Loots GG, Ovcharenko I, Pachter L, Dubchak I, Rubin EM (2002) rVista for comparative sequence-based discovery of functional transcription factor binding sites. Genome Res 12(5): 832–839

    PubMed  Google Scholar 

  • Markstein M, Markstein P, Markstein V, Levine MS (2002) Genome-wide analysis of clustered dorsal binding sites identifies putative target genes in the Drosophila embryo. Proc Natl Acad Sci USA 99(2):763–768

    Article  CAS  PubMed  Google Scholar 

  • McCue L, Thompson W, Carmack C, Ryan MP, Liu JS, Derbyshire V, Lawrence CE (2001) Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes. Nucleic Acids Res 29(3):774–782

    CAS  PubMed  Google Scholar 

  • McCue LA, Thompson W, Carmack CS, Lawrence CE (2002) Factors influencing the identification of transcription factor binding sites by cross-species comparison. Genome Res 12(10):1523–1532

    Article  CAS  PubMed  Google Scholar 

  • McGuire AM, Hughes JD, Church GM (2000) Conservation of DNA regulatory motifs and discovery of new motifs in microbial genomes. Genome Res 10(6):744–757

    Article  CAS  PubMed  Google Scholar 

  • McNally JG, Muller WG, Walker D, Wolford R, Hager GL (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287(5456):1262–1265

    Article  CAS  PubMed  Google Scholar 

  • Michelson AM (2002) Deciphering genetic regulatory codes: a challenge for functional genomics. Proc Natl Acad Sci USA 99:546–548

    Article  CAS  PubMed  Google Scholar 

  • Ohler U, Niemann H (2001) Identification and analysis of eukaryotic promoters: recent computational approaches. Trends Genet 17(2):56–60

    Article  CAS  PubMed  Google Scholar 

  • Ohler U, Niemann H, Liao GC, Rubin GM (2001) Joint modeling of DNA sequence and physical properties to improve eukaryotic promoter recognition. Bioinformatics 17 [suppl 1]:S199–S206

    Google Scholar 

  • Pearce D, Matsui W, Miner JN, Yamamoto KR (1998) Glucocorticoid receptor transcriptional activity determined by spacing of receptor and non-receptor DNA sites. J Biol Chem 273:30081–30085

    Article  CAS  PubMed  Google Scholar 

  • Pedersen AG, Baldi P, Chauvin Y, Brunak S (1999) The biology of eukaryotic promoter predictiona review. Comput Chem 23(3–4):191–207

    Google Scholar 

  • Polach KJ, Widom J (1995) Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation. J Mol Biol 254(2):130–149

    Article  CAS  PubMed  Google Scholar 

  • Polach KJ, Widom J (1996) A model for the cooperative binding of eukaryotic regulatory proteins to nucleosomal target sites. J Mol Biol 258(5):800–812

    Article  CAS  PubMed  Google Scholar 

  • Rajewsky N, Socci ND, Zapotocky M, Siggia ED (2002a) The evolution of DNA regulatory regions for proteo-gamma bacteria by interspecies comparisons. Genome Res 12(2):298–308

    CAS  PubMed  Google Scholar 

  • Rajewsky N, Vergassola M, Gaul U, Siggia ED (2002b) Computational detection of genomic cis-regulatory modules applied to body patterning in the early Drosophila embryo. BMC Bioinformatics 3(1):30

    Article  PubMed  Google Scholar 

  • Ren B, Robert F, Wyrick JJ, Aparicio O, Jennings EG, Simon I, Zeitlinger J, Schreiber J, Hannett N, Kanin E, Volkert TL, Wilson CJ, Bell SP, Young RA (2000) Genome-wide location and function of DNA binding proteins. Science 290(5500):2306–2309

    Article  CAS  PubMed  Google Scholar 

  • Roth FP, Hughes JD, Estep PW, Church GM (1998) Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation. Nat Biotechnol 16(10):939–945

    Google Scholar 

  • Roulet E, Busso S, Camargo AA, Simpson AJ, Mermod N, Bucher P (2002) High-throughput SELEX SAGE method for quantitative modeling of transcription-factor binding sites. Nat Biotechnol 20(8):831–835

    CAS  PubMed  Google Scholar 

  • Roy PJ, Stuart JM, Lund J, Kim SK (2002) Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans. Nature 418(6901):975–979

    Article  CAS  PubMed  Google Scholar 

  • Scherf M, Klingenhoff A, Frech K, Quandt K, Schneider R, Grote K, Frisch M, Gailus-Durner V, Seidel A, Brack-Werner R, Werner T (2001) First pass annotation of promoters on human chromosome 22. Genome Res 11(3):333–340

    Article  CAS  PubMed  Google Scholar 

  • Schneider TD, Stephens RM (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18(20):6097–6100

    CAS  PubMed  Google Scholar 

  • Shannon CE (1948) A mathematical theory of communication. Bell Syst Tech J 27:379–423, 623–56

    Google Scholar 

  • Shim EY, Woodcock C, Zaret KS (1998) Nucleosome positioning by the winged helix transcription factor HNF3. Genes Dev 12:5–10

    CAS  PubMed  Google Scholar 

  • Simpson ER, Michael MD, Agarwal VR, Hinshelwood MM, Bulun SE, Zhao Y (1997) Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage. FASEB J 11(1):29–36

    CAS  PubMed  Google Scholar 

  • Skalnikova M, Kozubek S, Lukasova E, Bartova E, Jirsova P, Cafourkova A, Koutna I, Kozubek M (2000) Spatial arrangement of genes, centromeres and chromosomes in human blood cell nuclei and its changes during the cell cycle, differentiation and after irradiation. Chromosome Res 8(6):487–499

    PubMed  Google Scholar 

  • Smale ST (1997) Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochim Biophys Acta 1351(1–2):73–88

    Google Scholar 

  • Spellman PT, Rubin GM (2002) Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 1(1):5

    Article  PubMed  Google Scholar 

  • Stormo GD (2000) DNA binding sites: representation and discovery. Bioinformatics 16(1):16–23

    Google Scholar 

  • Stormo GD, Fields DS (1998) Specificity, free energy and information content in protein-DNA interactions. Trends Biochem Sci 23:109–113

    Article  CAS  PubMed  Google Scholar 

  • Stormo GD, Tan K (2002) Mining genome databases to identify and understand new gene regulatory systems. Curr Opin Microbiol 5(2):149–153

    Article  CAS  PubMed  Google Scholar 

  • Tan K, Moreno-Hagelsieb G, Collado-Vides J, Stormo GD (2001) A comparative genomics approach to prediction of new members of regulons. Genome Res 11(4):566–584

    Article  CAS  PubMed  Google Scholar 

  • Tautz D (2000) Evolution of transcriptional regulation. Curr Opin Genet Dev 10(5):575–579

    Article  CAS  PubMed  Google Scholar 

  • Thijs G, Moreau Y, De Smet F, Mathys J, Lescot M, Rombauts S, Rouzé P, De Moor B, Marchal K (2002a) INCLUSive: integrated clustering, upstream sequence retrieval and motif sampling. Bioinformatics 18(2):331–332

    Article  CAS  PubMed  Google Scholar 

  • Thijs G, Marchal K, Lescot M, Rombauts S, De Moor B, Rouze P, Moreau Y (2002b) A Gibbs sampling method to detect overrepresented motifs in the upstream regions of coexpressed genes. J Comput Biol 9(2):447–464

    Article  PubMed  Google Scholar 

  • Tronche F, Ringeisen F, Blumenfeld M, Yaniv M, Pontoglio M (1997) Analysis of the distribution of binding sites for a tissue-specific transcription factor in the vertebrate genome. J Mol Biol 266(2):231–245

    Article  CAS  PubMed  Google Scholar 

  • Udalova IA, Mott R, Field D, Kwiatkowski D (2002) Quantitative prediction of NF-kappa B DNA-protein interactions. Proc Natl Acad Sci USA 99(12):8167–8172

    Article  CAS  PubMed  Google Scholar 

  • Wagner A (1999) Genes regulated cooperatively by one or more transcription factors and their identification in whole eukaryotic genomes. Bioinformatics 15(10):776–784

    Article  CAS  PubMed  Google Scholar 

  • Wasserman WW, Fickett JW (1998) Identification of regulatory regions which confer muscle-specific gene expression. J Mol Biol 278(1):167–181

    Article  CAS  PubMed  Google Scholar 

  • Wasserman WW, Palumbo M, Thompson W, Fickett JW, Lawrence CE (2000) Human–mouse genome comparisons to locate regulatory sites. Nat Genet 26:225–228

    Article  CAS  PubMed  Google Scholar 

  • Werner T (1999) Models for prediction and recognition of eukaryotic promoters. Mamm Genome 10(2):168–175

    Article  CAS  PubMed  Google Scholar 

  • Wolberger C (1999) Multiprotein–DNA complexes in transcriptional regulation. Annu Rev Biophys Biomol Struct 28:29–56

    Article  CAS  PubMed  Google Scholar 

  • Wolffe AP, Guschin D (2000) Review: chromatin structural features and targets that regulate transcription. J Struct Biol 129(2–3):102–122

    Google Scholar 

  • Workman CT, Stormo GD (2000) ANN-Spec: a method for discovering transcription factor binding sites with improved specificity. Proc Pac Symp Biocomputing 2000:467–478

    Google Scholar 

  • Wu J, Grunstein M (2000) 25 years after the nucleosome model: chromatin modifications. Trends Biochem Sci 25(12):619–623

    Article  CAS  PubMed  Google Scholar 

  • Xing EP, Wu W, Karp RM (2003) Capturing characteristic structural features for motif detection using a hierarchical Bayesian Markovian model. Genome Biol

  • Zhu JL, Kaytor EN, Pao CI, Meng XP, Phillips LS (2000) Involvement of Sp1 in the transcriptional regulation of the rat insulin-like growth factor-1 gene. Mol Cell Endocrinol 164:205–218

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful for suggestions from David A. Adler, James L. Holloway, Charles E. Lawrence, Richard H. Price, Gary D. Stormo, Marissa Vignali, and the members of the Wasserman research group. We are indebted to Carol Sattler for providing the electron micrograph in the background of Fig. 1, which was created by Edward J. Andrews (SomeLabDesign, Seattle, WA, USA). We also thank David A. Adler for help with Fig. 1.

Author information

Authors and Affiliations

  1. Centre for Molecular Medicine and Therapeutics (CMMT), University of British Columbia, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada

    Wyeth W. Wasserman

  2. ZymoGenetics, 1201 Eastlake Avenue East, Seattle, WA 98102, USA

    William Krivan

Authors
  1. Wyeth W. Wasserman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Krivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wyeth W. Wasserman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wasserman, W.W., Krivan, W. In silico identification of metazoan transcriptional regulatory regions. Naturwissenschaften 90, 156–166 (2003). https://doi.org/10.1007/s00114-003-0409-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00114-003-0409-4

Keywords

Search

Navigation