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Essentials of Bioinformatics, Volume II pp 283–299Cite as

Understanding the Regulatory Features of Co-regulated Genes Using Distant Regulatory Elements (DiRE) Genomic Tool in Health and Disease

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Abstract

Regulation of gene expression is a complex process which require several players working together in different time and space in a cell or tissue level. In eukaryotes, gene expression regulation is maintained by a complicated dynamic interplay between proximal promoters and distal regulatory elements (REs) such as repressors and enhancers and transcription factors (TFs). TFs are an important regulator of various life processes and diseases. Ample evidence now suggests that the regulatory networks and the interactions between target binding sites and various TFs play pivotal role in several diseases including cancers. TFs also play a key role in differential gene expression which has proven important in understanding the biological differences between healthy and diseased states. In this book chapter, we discuss about a genomic tool named DiRE which can predict distant REs based on transcription factor binding sites (TFBSs). It possesses a unique capacity to detect REs beyond regions of proximal promoter. DiRE can predict common REs in the coregulated genes. Here we describe step by step method to use this tool. At last, we also discuss the advantages and possible limitation of this tool use for genomic applications.

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Abbreviations

DEG:

Differentially Expressed Gene

DiRE:

Distant Regulatory Elements

ECR:

Evolutionary Conserved Region

EI:

Enhancer Identification

GWAS:

Genome-Wide Association Studies

RE:

Regulatory Elements

TF:

Transcription Factor

TFBS:

Transcription Factor Binding Site

TSS:

Transcriptional Start Site

UTR:

Untranslated Regions

References

  • Aid-Pavlidis T, Pavlidis P, Timmusk T (2009) Meta-coexpression conservation analysis of microarray data: a “subset” approach provides insight into brain-derived neurotrophic factor regulation. BMC Genomics 10:420

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Altermann E, Klaenhammer TR (2005) PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. BMC Genomics 6:60

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25(1):25–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baty F, Rüdiger J, Miglino N, Kern L, Borger P, Brutsche M (2013) Exploring the transcription factor activity in high-throughput gene expression data using RLQ analysis. BMC Bioinformatics 14:178

    Article  PubMed  PubMed Central  Google Scholar 

  • Bryne JC, Valen E, Tang MH, Marstrand T, Winther O, da Piedade I et al (2008) JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update. Nucleic Acids Res 36(Database issue):D102–D106

    CAS  PubMed  Google Scholar 

  • Campbell SJ, Gaulton A, Marshall J, Bichko D, Martin S, Brouwer C et al (2010) Visualizing the drug target landscape. Drug Discov Today 15(1–2):3–15

    Article  CAS  PubMed  Google Scholar 

  • Carroll SB (2008) Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 134(1):25–36

    Article  CAS  PubMed  Google Scholar 

  • Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M (2009) Mapping complex disease traits with global gene expression. Nat Rev Genet 10(3):184–194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK et al (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8(5):e1000384

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dimas AS, Deutsch S, Stranger BE, Montgomery SB, Borel C, Attar-Cohen H et al (2009) Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 325(5945):1246–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dottorini T, Palladino P, Senin N, Persampieri T, Spaccapelo R, Crisanti A (2013) CluGene: a bioinformatics framework for the identification of co-localized, co-expressed and co-regulated genes aimed at the investigation of transcriptional regulatory networks from high-throughput expression data. PLoS One 8(6):e66196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95(25):14863–14868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotea V, Ovcharenko I (2008) DiRE: identifying distant regulatory elements of co-expressed genes. Nucleic Acids Res 36(Web Server issue):W133–W139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harismendy O, Notani D, Song X, Rahim NG, Tanasa B, Heintzman N et al (2011) 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature 470(7333):264–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Liu J, Zhao Z, Zhao H (2017) Bioinformatics analysis of gene expression profiles of esophageal squamous cell carcinoma. Dis Esophagus 30(5):1–8

    Article  CAS  PubMed  Google Scholar 

  • Heyer LJ, Kruglyak S, Yooseph S (1999) Exploring expression data: identification and analysis of coexpressed genes. Genome Res 9(11):1106–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465(7295):182–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleinjan DA, van Heyningen V (2005) Long-range control of gene expression: emerging mechanisms and disruption in disease. Am J Hum Genet 76(1):8–32

    Article  CAS  PubMed  Google Scholar 

  • Koch F, Fenouil R, Gut M, Cauchy P, Albert TK, Zacarias-Cabeza J et al (2011) Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nat Struct Mol Biol 18(8):956–963

    Article  CAS  PubMed  Google Scholar 

  • Lam MT, Cho H, Lesch HP, Gosselin D, Heinz S, Tanaka-Oishi Y et al (2013) Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature 498(7455):511–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lenhard B, Sandelin A, Carninci P (2012) Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat Rev Genet 13(4):233–245

    Article  CAS  PubMed  Google Scholar 

  • Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA et al (2003) A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 12(14):1725–1735

    Article  CAS  PubMed  Google Scholar 

  • Loging W, Harland L, Williams-Jones B (2007) High-throughput electronic biology: mining information for drug discovery. Nat Rev Drug Discov 6(3):220–230

    Article  CAS  PubMed  Google Scholar 

  • Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM et al (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288(5463):136–140

    Article  CAS  PubMed  Google Scholar 

  • Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV et al (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466(7307):714–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobrega MA, Ovcharenko I, Afzal V, Rubin EM (2003) Scanning human gene deserts for long-range enhancers. Science 302(5644):413

    Article  CAS  PubMed  Google Scholar 

  • Ovcharenko I, Nobrega MA, Loots GG, Stubbs L (2004) ECR browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes. Nucleic Acids Res 32(Web Server issue):W280–W286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M et al (2006) In vivo enhancer analysis of human conserved non-coding sequences. Nature 444(7118):499–502

    Article  CAS  PubMed  Google Scholar 

  • Pennacchio LA, Loots GG, Nobrega MA, Ovcharenko I (2007) Predicting tissue-specific enhancers in the human genome. Genome Res 17(2):201–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H et al (2009) The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 41(8):882–884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez-Esteban R, Jiang X (2017) Differential gene expression in disease: a comparison between high-throughput studies and the literature. BMC Med Genet 10(1):59

    Google Scholar 

  • Roy AL, Singer DS (2015) Core promoters in transcription: old problem, new insights. Trends Biochem Sci 40(3):165–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakabe NJ, Savic D, Nobrega MA (2012) Transcriptional enhancers in development and disease. Genome Biol 13(1):238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sauna ZE, Kimchi-Sarfaty C (2011) Understanding the contribution of synonymous mutations to human disease. Nat Rev Genet 12(10):683–691

    Article  CAS  PubMed  Google Scholar 

  • Schor IE, Degner JF, Harnett D, Cannavò E, Casale FP, Shim H et al (2017) Promoter shape varies across populations and affects promoter evolution and expression noise. Nat Genet 49(4):550–558

    Article  CAS  PubMed  Google Scholar 

  • Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB et al (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9(12):3273–3297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stranger BE, Stahl EA, Raj T (2011) Progress and promise of genome-wide association studies for human complex trait genetics. Genetics 187(2):367–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuan D, Kong S, Hu K (1992) Transcription of the hypersensitive site HS2 enhancer in erythroid cells. Proc Natl Acad Sci U S A 89(23):11219–11223

    Article  CAS  Google Scholar 

  • Vo Ngoc L, Wang YL, Kassavetis GA, Kadonaga JT (2017) The punctilious RNA polymerase II core promoter. Genes Dev 31(13):1289–1301

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420(6915):520–562

    Article  CAS  PubMed  Google Scholar 

  • Wingender E, Dietze P, Karas H, Knüppel R (1996) TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res 24(1):238–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wingender E, Chen X, Hehl R, Karas H, Liebich I, Matys V et al (2000) TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res 28(1):316–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yáñez-Cuna JO, Kvon EZ, Stark A (2013) Deciphering the transcriptional cis-regulatory code. Trends Genet 29(1):11–22

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Biology Department, Faculty of Sciences, University of Jeddah, Jeddah, Saudi Arabia

    Arif Mohammed & Othman A. Alghamdi

  2. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohd Rehan

  3. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohd Rehan

  4. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Babajan Banaganapalli, Ramu Elango & Noor Ahmad Shaik

Authors
  1. Arif Mohammed
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  2. Othman A. Alghamdi
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  3. Mohd Rehan
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  4. Babajan Banaganapalli
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  5. Ramu Elango
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  6. Noor Ahmad Shaik
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Corresponding authors

Correspondence to Arif Mohammed or Noor Ahmad Shaik .

Editor information

Editors and Affiliations

  1. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Noor Ahmad Shaik

  2. Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Khalid Rehman Hakeem

  3. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Babajan Banaganapalli

  4. Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Ramu Elango

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Mohammed, A., Alghamdi, O.A., Rehan, M., Banaganapalli, B., Elango, R., Shaik, N.A. (2019). Understanding the Regulatory Features of Co-regulated Genes Using Distant Regulatory Elements (DiRE) Genomic Tool in Health and Disease. In: Shaik, N., Hakeem, K., Banaganapalli, B., Elango, R. (eds) Essentials of Bioinformatics, Volume II. Springer, Cham. https://doi.org/10.1007/978-3-030-18375-2_13

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