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Coordinated Networks of microRNAs and Transcription Factors with Evolutionary Perspectives

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 774)

Abstract

MicroRNAs (miRNAs) and transcription factors (TFs) are two major classes of trans-regulators in gene regulatory networks. Coordination between miRNAs and TFs has been demonstrated by individual studies on developmental processes and the pathogenesis of various cancers. Systematic computational approaches have an advantage in elucidating global network features of the miRNA-TF coordinated regulation. miRNAs and TFs have distinct molecular and evolutionary properties. In particular, miRNA genes have a rapid turnover of birth-and-death processes during evolution, and their effects are widespread but modest. Therefore, miRNAs and TFs are considered to have different contributions to their coordination. The miRNA-TF coordinated feedforward circuits are considered to cause significant increases in redundancy but drastically reduce the target gene repertoire, which poses the question, to what extent is miRNA-TF coordination beneficial? Evolutionary analyses provide wide perspectives on the features of miRNA-TF coordinated regulatory networks at a systems level.

Keywords

MicroRNA Transcription factor Coordinated regulation, regulatory network Redundancy Natural selection 

Abbreviations

miRNA

microRNA

TF

transcription factor

TFBS

transcription factor binding site

PSSM

position-specific scoring matrix

PWM

position-weight matrix

pri-miRNA

primary miRNA

pre-miRNA

precursor miRNA

RISC

RNA-induced silencing complex

UTR

untranslated region

HITS-CLIP

high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation

PAR-CLIP

photoactivatable-ribonucleoside-enhanced crosslinking and immuno­precipitation

TE

transposable element

MITE

miniature inverted-repeat transposable element

Myr

million years

GO

Gene Ontology

FFL

feedforward loop

FFC

feedforward circuit

Y1H

yeast one-hybrid

Notes

Acknowledgment

This work was supported by Grant-in-Aid for Scientific Research (MEXT) KAKENHI 23570273.

References

  1. 1.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854PubMedGoogle Scholar
  2. 2.
    Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862PubMedGoogle Scholar
  3. 3.
    Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39(Database Issue):D152–D157PubMedCentralPubMedGoogle Scholar
  4. 4.
    Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36(Database Issue):D154–D158PubMedCentralPubMedGoogle Scholar
  5. 5.
    Griffiths-Jones S (2004) The microRNA registry. Nucleic Acids Res 32(Database Issue):D109–D111PubMedCentralPubMedGoogle Scholar
  6. 6.
    Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10(4):252–63PubMedGoogle Scholar
  7. 7.
    Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20PubMedGoogle Scholar
  8. 8.
    Sandelin A, Alkema W, Engstrom P, Wasserman WW, Lenhard B (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res 32(Database issue):D91–94PubMedCentralPubMedGoogle Scholar
  9. 9.
    Bryne JC, Valen E, Tang MH, Marstrand T, Winther O, da Piedade I, Krogh A, Lenhard B, Sandelin A (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):D102–106PubMedCentralPubMedGoogle Scholar
  10. 10.
    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):238–241PubMedCentralPubMedGoogle Scholar
  11. 11.
    Matys V et al (2006) Transfac and its module transcompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 34(Database issue):108–110Google Scholar
  12. 12.
    Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060PubMedGoogle Scholar
  13. 13.
    Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425(6956):415–419PubMedGoogle Scholar
  14. 14.
    MacRae I, Zhou K, Li F, Repic A, Brooks A, Cande W, Adams P, Doudna J (2006) Structural basis for double-stranded RNA processing by Dicer. Science 311(5758):195–198PubMedGoogle Scholar
  15. 15.
    Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123(4):631–640PubMedGoogle Scholar
  16. 16.
    Stark A, Kheradpour P, Parts L, Brennecke J, Hodges E, Hannon GJ, Kellis M (2007) Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes. Genome Res 17(12):1865–1879PubMedGoogle Scholar
  17. 17.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedGoogle Scholar
  18. 18.
    Mallory AC, Reinhart BJ, Jones-Rhoades MW, Tang G, Zamore PD, Barton MK, Bartel DP (2004) MicroRNA control of PHABULOSA in leaf development: importance of pairing to the microRNA 5′ region. EMBO J 23(16):3356–3364PubMedGoogle Scholar
  19. 19.
    McDowall J, Hunter S (2011) InterPro protein classification. Methods Mol Biol 694:37–47PubMedGoogle Scholar
  20. 20.
    Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Das U, Daugherty L, Duquenne L, Finn RD, Gough J, Haft D, Hulo N, Kahn D, Kelly E, Laugraud A, Letunic I, Lonsdale D, Lopez R, Madera M, Maslen J, McAnulla C, McDowall J, Mistry J, Mitchell A, Mulder N, Natale D, Orengo C, Quinn AF, Selengut JD, Sigrist CJ, Thimma M, Thomas PD, Valentin F, Wilson D, Wu CH, Yeats C (2009) InterPro: the integrative protein signature database. Nucleic Acids Res 37(Database issue):D211–215PubMedCentralPubMedGoogle Scholar
  21. 21.
    Kummerfeld SK, Teichmann SA (2006) DBD: a transcription factor prediction database. Nucleic Acids Res 34(Database issue):D74–D81PubMedCentralPubMedGoogle Scholar
  22. 22.
    Reece-Hoyes JS, Deplancke B, Shingles J, Grove CA, Hope IA et al (2005) A compendium of C. elegans regulatory transcription factors: a resource for mapping transcription regulatory networks. Genome Biol 6:R110PubMedCentralPubMedGoogle Scholar
  23. 23.
    Bentwich I et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37(7):766–770PubMedGoogle Scholar
  24. 24.
    Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 30(1):89–100Google Scholar
  25. 25.
    Berezikov E, Chung W, Willis J, Cuppen E, Lai E (2007) Mammalian mirtron genes. Mol Cell 28(2):328–336PubMedCentralPubMedGoogle Scholar
  26. 26.
    Rajewsky N (2006) microRNA target predictions in animals. Nat Genet 38(Suppl):S8–S13PubMedGoogle Scholar
  27. 27.
    Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–5PubMedGoogle Scholar
  28. 28.
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080PubMedGoogle Scholar
  29. 29.
    Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39(10):1278–1284PubMedGoogle Scholar
  30. 30.
    Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27(1):91–105PubMedCentralPubMedGoogle Scholar
  31. 31.
    Iwama H, Masaki T, Kuriyama S (2007) Abundance of microRNA target motifs in the 3’-UTRs of 20527 human genes. FEBS Lett 581(9):1805–1810PubMedGoogle Scholar
  32. 32.
    Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455(7216):1124–1128PubMedGoogle Scholar
  33. 33.
    Lal A, Navarro F, Maher CA, Maliszewski LE, Yan N, O’Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofmann O, Becker KG, Gorospe M, Hide W, Lieberman J (2009) miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3’UTR microRNA recognition elements. Mol Cell 35(5):610–625PubMedCentralPubMedGoogle Scholar
  34. 34.
    Thomas M, Lieberman J, Lal A (2010) Desperately seeking microRNA targets. Nat Struct Mol Biol 17(10):1169–1174PubMedGoogle Scholar
  35. 35.
    Mangone M, Manoharan AP, Thierry-Mieg D, Thierry-Mieg J, Han T, Mackowiak SD, Mis E, Zegar C, Gutwein MR, Khivansara V, Attie O, Chen K, Salehi-Ashtiani K, Vidal M, Harkins TT, Bouffard P, Suzuki Y, Sugano S, Kohara Y, Rajewsky N, Piano F, Gunsalus KC, Kim JK (2010) The landscape of C. elegans 3’UTRs. Science 329(5990):432–435PubMedCentralPubMedGoogle Scholar
  36. 36.
    Jan CH, Friedman RC, Ruby JG, Bartel DP (2011) Formation, regulation and evolution of Caeno­rhabditis elegans 3’UTRs. Nature 469(7328):97–101PubMedCentralPubMedGoogle Scholar
  37. 37.
    Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310(5755):1817–1821PubMedGoogle Scholar
  38. 38.
    Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460(7254):479–486PubMedCentralPubMedGoogle Scholar
  39. 39.
    Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp AC, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141(1):129–141PubMedCentralPubMedGoogle Scholar
  40. 40.
    Tanzer A, Stadler PF (2004) Molecular evolution of a microRNA cluster. J Mol Biol 339(2):327–335PubMedGoogle Scholar
  41. 41.
    Zhang R, Peng Y, Wang W, Su B (2007) Rapid evolution of an X-linked microRNA cluster in primates. Genome Res 17(5):612–617PubMedGoogle Scholar
  42. 42.
    Li J, Liu Y, Dong D, Zhang Z (2010) Evolution of an X-linked primate-specific micro RNA cluster. Mol Biol Evol 27(3):671–683PubMedGoogle Scholar
  43. 43.
    Fahlgren N, Howell MD, Kasschau KD, Chapman EJ, Sullivan CM, Cumbie JS, Givan SA, Law TF, Grant SR, Dangl JL, Carrington JC (2007) High-throughput sequencing of Arabidopsis microRNAs: evidence for frequent birth and death of miRNA genes. PLoS One 2(2):e219PubMedCentralPubMedGoogle Scholar
  44. 44.
    Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC (2004) Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nat Genet 36(12):1282–1290PubMedGoogle Scholar
  45. 45.
    Piriyapongsa J, Marino-Ramirez L, Jordan IK (2007) Origin and evolution of human microRNAs from transposable elements. Genetics 176(2):1323–1337PubMedGoogle Scholar
  46. 46.
    Piriyapongsa J, Jordan IK (2008) Dual coding of siRNAs and miRNAs by plant transposable elements. RNA 14(5):814–821PubMedGoogle Scholar
  47. 47.
    Piriyapongsa J, Jordan IK (2007) A family of human microRNA genes from miniature inverted-repeat transposable elements. PLoS One 2(2):e203PubMedCentralPubMedGoogle Scholar
  48. 48.
    Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005) The transcriptional landscape of the mammalian genome. Science 309(5740):1559–1563Google Scholar
  49. 49.
    Manak JR, Dike S, Sementchenko V, Kapranov P, Biemar F, Long J, Cheng J, Bell I, Ghosh S, Piccolboni A, Gingeras TR (2006) Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nat Genet 38(10):1151–1158PubMedGoogle Scholar
  50. 50.
    Lu J, Shen Y, Wu Q, Kumar S, He B, Shi S, Carthew RW, Wang SM, Wu CI (2008) The birth and death of microRNA genes in Drosophila. Nat Genet 40(3):351–355PubMedGoogle Scholar
  51. 51.
    Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M, Hannon GJ, Lai EC (2010) Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nat Genet 42(1):6–9PubMedGoogle Scholar
  52. 52.
    Lu J, Shen Y, Carthew RW, San MW, Wu C-I (2010) Reply to “Evolutionary flux of canonical microRNAs and mirtrons in Drosophila”. Nat Genet 42(1):9–10Google Scholar
  53. 53.
    Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 39:121–152PubMedCentralPubMedGoogle Scholar
  54. 54.
    Wu CI, Shen Y, Tang T (2009) Evolution under canalization and the dual roles of microRNAs: a hypothesis. Genome Res 19(5):734–743PubMedGoogle Scholar
  55. 55.
    Liang H, Li WH (2009) Lowly expressed human microRNA genes evolve rapidly. Mol Biol Evol 26(6):1195–1198PubMedGoogle Scholar
  56. 56.
    Lu J, Fu Y, Kumar S, Shen Y, Zeng K, Xu A, Carthew R, Wu CI (2008) Adaptive evolution of newly emerged micro-RNA genes in Drosophila. Mol Biol Evol 25(5):929–938PubMedGoogle Scholar
  57. 57.
    Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Combinatorial microRNA target predictions. Nat Genet 37(5):495–500PubMedGoogle Scholar
  58. 58.
    Eisenberg E, Levanon EY (2003) Human housekeeping genes are compact. Trends Genet 19(7):362–365PubMedGoogle Scholar
  59. 59.
    Miska EA, Alvarez-Saavedra E, Abbott AL, Lau NC, Hellman AB, McGonagle SM, Bartel DP, Ambros VR, Horvitz HR (2007) Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet 3(12):e215PubMedCentralPubMedGoogle Scholar
  60. 60.
    Nakahara K, Kim K, Sciulli C, Dowd SR, Minden JS, Carthew RW (2005) Targets of microRNA regulation in the Drosophila oocyte proteome. Proc Natl Acad Sci USA 102(34):12023–12028PubMedGoogle Scholar
  61. 61.
    Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455(7209):58–63PubMedGoogle Scholar
  62. 62.
    Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455(7209):64–71PubMedCentralPubMedGoogle Scholar
  63. 63.
    Lynch M (2007) The evolution of genetic networks by non-adaptive processes. Nat Rev Genet 8(10):803–813PubMedGoogle Scholar
  64. 64.
    Lynch M (2007) The frailty of adaptive hypotheses for the origins of organismal complexity. Proc Natl Acad Sci USA 104(Suppl 1):8597–8604PubMedGoogle Scholar
  65. 65.
    Zuckerkandl E (1997) Neutral and nonneutral mutations: the creative mix–evolution of complexity in gene interaction systems. J Mol Evol 44(4):470PubMedGoogle Scholar
  66. 66.
    Alon U (2006) Introduction to systems biology: design principles of biological circuits. CRC Press, Boca RatonGoogle Scholar
  67. 67.
    Shen-Orr SS, Milo R, Mangan S, Alon U (2002) Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 31:64–68PubMedGoogle Scholar
  68. 68.
    Milo R et al (2002) Network motifs: simple building blocks of complex networks. Science 298(5594):824–827PubMedGoogle Scholar
  69. 69.
    Alon U (2007) Network motifs: theory and experimental approaches. Nat Rev Genet 8(6):450–461PubMedGoogle Scholar
  70. 70.
    Newman ME, Strogatz SH, Watts DJ (2001) Random graphs with arbitrary degree distributions and their applications. Phys Rev E 64:026118Google Scholar
  71. 71.
    Milo R, Itzkovitz S, Kashtan N, Levitt R, Shen-Orr S, Ayzenshtat I, Sheffer M, Alon U (2004) Superfamilies of evolved and designed networks. Science 303(5663):1538–1542PubMedGoogle Scholar
  72. 72.
    Tsang J, Zhu J, van Oudenaarden A (2007) MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell 26(5):753–767PubMedCentralPubMedGoogle Scholar
  73. 73.
    Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC (2005) Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci USA 102(50):18017–18022PubMedGoogle Scholar
  74. 74.
    Baskerville S, Bartel DP (2005) Microarray profiling of micro-RNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11(3):241–247PubMedGoogle Scholar
  75. 75.
    Li X, Carthew RW (2005) A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell 123(7):1267–1277PubMedGoogle Scholar
  76. 76.
    Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10):1902–1910PubMedGoogle Scholar
  77. 77.
    Sugino K, Hempel CM, Miller MN, Hattox AM, Shapiro P, Wu C, Huang ZJ, Nelson SB (2006) Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat Neurosci 9(1):99–107PubMedGoogle Scholar
  78. 78.
    Arlotta P, Molyneaux BJ, Chen J, Inoue J, Kominami R, Macklis JD (2005) Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron 45(2):207–221PubMedGoogle Scholar
  79. 79.
    Shalgi R, Lieber D, Oren M, Pilpel Y (2007) Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol 3(7):e131PubMedCentralPubMedGoogle Scholar
  80. 80.
    Hornstein E, Shomron N (2006) Canalization of development by microRNAs. Nat Genet 38(Suppl):S20–24PubMedGoogle Scholar
  81. 81.
    Friedman RC, Farh KK-H, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of MicroRNAs. Genome Res 19(1):92–105PubMedGoogle Scholar
  82. 82.
    Chen K, Rajewsky N (2006) Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet 38(12):1452–1456PubMedGoogle Scholar
  83. 83.
    Iwama H, Gojobori T (2004) Highly conserved upstream sequences for transcription factor genes and implications for the regulatory network. Proc Natl Acad Sci USA 101(49):17156–17161PubMedGoogle Scholar
  84. 84.
    Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of Mammalian MicroRNA Targets. Cell 115(7):787–798PubMedGoogle Scholar
  85. 85.
    Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A et al (2004) MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 14(12):2486–2494PubMedGoogle Scholar
  86. 86.
    Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA et al (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 101(16):6062–6067PubMedGoogle Scholar
  87. 87.
    Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, Diekhans M, Dreszer TR, Giardine BM, Harte RA, Hillman-Jackson J, Hsu F, Kirkup V, Kuhn RM, Learned K, Li CH, Meyer LR, Pohl A, Raney BJ, Rosenbloom KR, Smith KE, Haussler D, Kent WJ (2011) The UCSC genome browser database: update 2011. Nucleic Acids Res 39(Database issue):D876–882PubMedCentralPubMedGoogle Scholar
  88. 88.
    Matys V, Fricke E, Geffers R, Gossling E, Haubrock M et al (2003) TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31(1):374–378PubMedCentralPubMedGoogle Scholar
  89. 89.
    Wingender E (2008) The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation. Brief Bioinform 9(4):326–332PubMedGoogle Scholar
  90. 90.
    Martinez NJ, Ow MC, Barrasa MI, Hammell M, Sequerra R, Doucette-Stamm L, Roth FP, Ambros VR, Walhout AJ (2008) A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity. Genes Dev 22(18):2535–2549PubMedGoogle Scholar
  91. 91.
    Barrasa MI, Vaglio P, Cavasino F, Jacotot L, Walhout AJM (2007) EDGEdb: a transcription factor–DNA interaction database for the analysis of C. elegans differential gene expression. BMC Genomics 8:21PubMedCentralPubMedGoogle Scholar
  92. 92.
    Deplancke B, Mukhopadhyay A, Ao W, Elewa AM, Grove CA, Martinez NJ, Sequerra R, Doucette-Stam L, Reece-Hoyes JS, Hope IA et al (2006) A gene-centered C. elegans protein–DNA interaction network. Cell 125(6):1193–1205PubMedGoogle Scholar
  93. 93.
    Vermeirssen V, Barrasa MI, Hidalgo C, Babon JAB, Sequerra R, Doucette-Stam L, Barabasi AL, Walhout AJM (2007) Transcription factor modularity in a gene-centered C. elegans core neuronal protein–DNA interaction network. Genome Res 17(7):1061–1071PubMedGoogle Scholar
  94. 94.
    Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003) miRanda algorithm: MicroRNA targets in Drosophila. Genome Biol 5(1):R1PubMedCentralPubMedGoogle Scholar
  95. 95.
    John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS (2004) Human MicroRNA targets. PLoS Biol 2(11):e363PubMedCentralPubMedGoogle Scholar
  96. 96.
    Betel D, Wilson M, Gabow A, Marks DS, Sander C (2008) microRNA target predictions: the microRNA.org resource: targets and expression. Nucleic Acids Res 36(Database Issue):D149–153PubMedCentralPubMedGoogle Scholar
  97. 97.
    Betel D, Koppal A, Agius P, Sander C, Leslie C (2010) mirSVR predicted target site scoring method: comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 11:R90PubMedCentralPubMedGoogle Scholar
  98. 98.
    Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R (2004) Fast and effective prediction of microRNA/target duplexes. RNA 10(10):1507–1517PubMedGoogle Scholar
  99. 99.
    Krüger J, Rehmsmeier M (2006) RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 34(Web Server issue):W451–454PubMedCentralPubMedGoogle Scholar
  100. 100.
    Grün D, Wang YL, Langenberger D, Gunsalus KC, Rajewsky N (2005) microRNA target predictions in seven Drosophila species. PLoS Comp Biol 1:e13Google Scholar
  101. 101.
    Lall S, Grün D, Krek A, Chen K, Wang YL, Dewey CN, Sood P, Colombo T, Bray N, Macmenamin P, Kao HL, Gunsalus KC, Pachter L, Piano F, Rajewsky N (2006) A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol 16(5):460–471PubMedGoogle Scholar
  102. 102.
    Yeger-Lotem E, Sattath S, Kashtan N, Itzkovitz S, Milo R, Pinter RY, Alon U, Margalit H (2004) Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. Proc Natl Acad Sci 101(16):5934–5939PubMedGoogle Scholar
  103. 103.
    Yu X, Lin J, Zack DJ, Mendell JT, Qian J (2008) Analysis of regulatory network topology reveals functionally distinct classes of microRNAs. Nucleic Acids Res 36(20):6494–6503PubMedCentralPubMedGoogle Scholar
  104. 104.
    Iwama H, Murao K, Imachi H, Ishida T (2011) Transcriptional double-autorepression feedforward circuits act for multicellularity and nervous system development. BMC Genomics 12:228PubMedCentralPubMedGoogle Scholar
  105. 105.
    Hollenhorst PC, Shah AA, Hopkins C, Graves BJ (2007) Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Genes Dev 21(15):1882–1894PubMedGoogle Scholar
  106. 106.
    Ow MC, Martinez NJ, Olsen PH, Silverman HS, Barrasa MI, Conradt B, Walhout AJ, Ambros V (2008) The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans. Genes Dev 22(18):2520–2534PubMedGoogle Scholar
  107. 107.
    Martinez NJ, Walhout AJ (2009) The interplay between transcription factors and microRNAs in genome-scale regulatory networks. Bioessays 31(4):435–445PubMedCentralPubMedGoogle Scholar
  108. 108.
    Bartel DP, Chen CZ (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5(5):396–400PubMedGoogle Scholar
  109. 109.
    Iwama H, Murao K, Imachi H, Ishida T (2011) MicroRNA networks alter to conform to transcription factor networks adding redundancy and reducing the repertoire of target genes for coordinated regulation. Mol Biol Evol 28(1):639–646PubMedGoogle Scholar
  110. 110.
    Iwama H, Hori Y, Matsumoto K, Murao K, Ishida T (2008) ReAlignerV: web-based genomic alignment tool with high specificity and robustness estimated by species-specific insertion sequences. BMC Bioinform 9:112Google Scholar
  111. 111.
    Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, MacDonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432(7014):226–230PubMedGoogle Scholar
  112. 112.
    Karres JS, Hilgers V, Carrers I, Treisman J, Cohen SM (2007) The conserved microRNA miR-8 tunes atrophin levels to prevent neurodegeneration in Drosophila. Cell 131(1):136–145PubMedGoogle Scholar
  113. 113.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233PubMedCentralPubMedGoogle Scholar
  114. 114.
    Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906PubMedGoogle Scholar
  115. 115.
    Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM (2005) Animal microRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123(6):1133–1146PubMedGoogle Scholar
  116. 116.
    Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, Baskerville S, Bartel DP, Tabin CJ (2005) The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature 438(7068):671–674PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Life Science Research CenterKagawa UniversityKagawaJapan
  2. 2.Faculty of MedicineKagawa UniversityKagawaJapan

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