Biopolym. Cell. 2015; 31(1):63-71.
Bioinformatics
Bioinformatics analysis of cis-regulatory elements in Mbl1 and Mbl2 genes in Rattus norvegicus
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - Educational and Scientific Center "Institute of Biology",
Taras Shevchenko National University of Kyiv
64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
Abstract
Aim. To identify and characterize with the help of bioinformatics the transcription factors binding sites in promoters of Mbl1 and Mbl2 genes, encoding mannose binding lectins in Rattus norvegicus. Methods. Bioinformatics, MatInspector software. The position weight matrices of transcription factor binding sites were obtained from the Matrix Family Library Version 9.0. Within the frame of the program we selected the binding sites, the cognate transcription factors of which are specifically expressed in the liver and immune cells, and have passed the filter for conservation after comparison with the binding sites in orthologous genes in Mus musculus. Results. The promoters of both genes share the binding sites for the members of the four common families of transcription factors (HNF, homeodomain transcription factors, GRs and ETS factors). The promoters of Mbl1 and Mbl2 gene possess correspondingly additional binding sites for the members of six (AP1 related factors, Ccaat/Enhancer Binding Proteins, FOX, p53, NFAT, ISGF3) and four (cAMP-responsive element binding proteins, heat shock factors, Nf-?B/c-rel and TATA binding protein) families of transcription factors. The Mbl1 specific transcription factors are mainly involved in the regulation of differentiation, development, metabolic homeostasis, organogenesis and cell cycle. Unlike them the Mbl2 specific transcription factors are more prone to mediate a stress-response. Conclusion. The variety of transcription factors potentially involved in regulation of the Mbl1 and Mbl2 transcription argue for these genes involvement in various cellular processes with specific role of each gene. The obtained results provide the basis for the task-oriented wet-lab bench experiments on their regulation.
Keywords: mannose binding lectins, position weight matrices, transcription factor binding sites
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Supplementary data
References
[1]
Turner MW. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today. 1996;17(11):532-40.
[2]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76.
[3]
Stuart LM, Takahashi K, Shi L, Savill J, Ezekowitz RA. Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J Immunol. 2005;174(6):3220-6.
[4]
Fujita T, Endo Y, Nonaka M. Primitive complement system--recognition and activation. Mol Immunol. 2004;41(2-3):103-11.
[5]
Matsushita M, Fujita T. Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med. 1992;176(6):1497-502.
[6]
Schwaeble W, Dahl MR, Thiel S, Stover C, Jensenius JC. The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin paÂthway activation complex encoded by two genes. Immunobiology. 2002; 205(4–5):455–66.
[7]
Takahashi K, Chang WC, Takahashi M, Pavlov V, Ishida Y, La Bonte L, Shi L, Fujita T, Stahl GL, Van Cott EM. Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation. Immunobiology. 2011;216(1-2):96-102.
[8]
Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-97.
[9]
Takahashi K, Ip WE, Michelow IC, Ezekowitz RA. The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol. 2006;18(1):16-23.
[10]
Farrar CA, Sacks SH. Mechanisms of rejection: role of complement. Curr Opin Organ Transplant. 2014;19(1):8-13.
[11]
Huber-Lang M, Kovtun A, Ignatius A. The role of complement in trauma and fracture healing. Semin Immunol. 2013;25(1):73-8.
[12]
Jha AN, Sundaravadivel P, Singh VK, Pati SS, Patra PK, Kremsner PG, Velavan TP, Singh L, Thangaraj K. MBL2 variations and malaria susceptibility in Indian populations. Infect Immun. 2014;82(1):52-61.
[13]
Herpers BL, Endeman H, de Jong BA, de Jongh BM, Grutters JC, Biesma DH, van Velzen-Blad H. Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes. Clin Exp Immunol. 2009;156(3):488-94.
[14]
Larghi EL, Kaufman TS. Modulators of complement activation: a patent review (2008 - 2013). Expert Opin Ther Pat. 2014;24(6):665-86.
[15]
Tokovenko BT, El’skaya AV, Obolenskaya MYu. In silico approach to study and functionally analyze interferon regulated genes. Biopolym Cell. 2007;23(4):368–75.
[16]
Tokovenko B, Golda R, Protas O, Obolenskaya M, El’skaya A. COTRASIF: conservation-aided transcription-factor-binding site finder. Nucleic Acids Res. 2009;37(7):e49.
[17]
Drahushchenko OO, Tokovenko BT, Obolens'ka MIu. [Initial analysis of the results of the genome-wide search for the genes responsive to interferon alpha]. Ukr Biokhim Zh. 2010;82(1):82-9.
[18]
Matsushita M, Hijikata M, Matsushita M, Ohta Y, Mishiro S. Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients. J Hepatol. 1998;29(5):695-700.
[19]
Quandt K, Frech K, Karas H, Wingender E, Werner T. MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 1995;23(23):4878-84.
[20]
Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, Frisch M, Bayerlein M, Werner T. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics. 2005;21(13):2933-42. ttp://
[22]
Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part I: the hepatocyte nuclear factor network and liver-specific gene expression. Pharmacol Rev. 2002;54(1):129-58.
[24]
Kassel O, Herrlich P. Crosstalk between the glucocorticoid receptor and other transcription factors: molecular aspects. Mol Cell Endocrinol. 2007;275(1-2):13-29.
[25]
Garrett-Sinha LA. Review of Ets1 structure, function, and roles in immunity. Cell Mol Life Sci. 2013;70(18):3375-90.
[26]
Yang TT, Chow CW. Transcription cooperation by NFAT.C/EBP composite enhancer complex. J Biol Chem. 2003;278(18):15874-85.
[27]
Marecki S, Riendeau CJ, Liang MD, Fenton MJ. PU.1 and multiple IFN regulatory factor proteins synergize to mediate transcriptional activation of the human IL-1 beta gene. J Immunol. 2001;166(11):6829-38.
[29]
Schrem H, Klempnauer J, Borlak J. Liver-enriched transcription factors in liver function and development. Part II: the C. EBPs and D site-binding protein in cell cycle control, carcinogenesis, circadian gene regulation, liver reÂgeneration, apoptosis, and liver-specific gene regulation. Pharmacol Rev. 2004;56(2):291–330.
[30]
Le Lay J, Kaestner KH. The Fox genes in the liver: from organogenesis to functional integration. Physiol Rev. 2010;90(1):1-22.
[31]
Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5(6):472-84.
[32]
Vaughan C, Pearsall I, Yeudall A, Deb SP, Deb S. p53: its mutations and their impact on transcription. Subcell Biochem. 2014;85:71-90.
[33]
Akerfelt M, Morimoto RI, Sistonen L. Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol. 2010;11(8):545-55.
[34]
Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 1999;68:821–61.
[35]
Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25(51):6680-4.
[37]
Basehoar AD, Zanton SJ, Pugh BF. Identification and distinct regulation of yeast TATA box-containing genes. Cell. 2004;116(5):699-709.
[38]
Zou Y, Huang W, Gu Z, Gu X. Predominant gain of promoter TATA box after gene duplication associated with stress responses. Mol Biol Evol. 2011;28(10):2893-904.
[39]
Han HW, Bae SH, Jung YH, Kim JH, Moon J. Genome-wide characterization of the relationship between essential and TATA-containing genes. FEBS Lett. 2013;587(5):444-51.
[40]
Guo N, Mogues T, Weremowicz S, Morton CC, Sastry KN. The human ortholog of rhesus mannose-binding protein-A gene is an expressed pseudogene that localizes to chromosome 10. Mamm Genome. 1998;9(3):246-9.
[41]
Lynch M, Conery JS. The evolutionary fate and consequences of duplicate genes. Science. 2000;290(5494):1151-5.
[42]
Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375-86.
[43]
Rutkowski MJ, Sughrue ME, Kane AJ, Ahn BJ, Fang S, Parsa AT. The complement cascade as a mediator of tissue growth and regeneration. Inflamm Res. 2010;59(11):897-905.
[44]
Rutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Fang S, Parsa AT. Complement and the central nervous system: emerging roles in development, protection and regeneration. Immunol Cell Biol. 2010;88(8):781-6.
[45]
Degnan BM, Degnan SM, Naganuma T, Morse DE. The ets multigene family is conserved throughout the Metazoa. Nucleic Acids Res. 1993;21(15):3479-84.
[46]
Degnan BM, Morse DE. Identification of eight homeobox-containing transcripts expressed during larval development and at metamorphosis in the gastropod mollusc Haliotis rufescens. Mol Mar Biol Biotechnol. 1993;2(1):1-9.
[47]
Baker ME, Funder JW, Kattoula SR. Evolution of hormone selectivity in glucocorticoid and mineralocorticoid receptors. J Steroid Biochem Mol Biol. 2013;137:57-70.
[48]
Amoutzias GD, Veron AS, Weiner J 3rd, Robinson-Rechavi M, Bornberg-Bauer E, Oliver SG, Robertson DL. One billion years of bZIP transcription factor evolution: conservation and change in dimerization and DNA-binding site specificity. Mol Biol Evol. 2007;24(3):827-35.
[49]
Rutkowski R, Hofmann K, Gartner A. Phylogeny and function of the invertebrate p53 superfamily. Cold Spring Harb Perspect Biol. 2010;2(7):a001131.
[50]
Shimeld SM, Degnan B, Luke GN. Evolutionary genomics of the Fox genes: origin of gene families and the ancestry of gene clusters. Genomics. 2010;95(5):256-60.
[51]
Song X, Hu J, Jin P, Chen L, Ma F. Identification and evolution of an NFAT gene involving Branchiostoma belcheri innate immunity. Genomics. 2013;102(4):355-62.
[52]
Langevin C, Aleksejeva E, Passoni G, Palha N, Levraud JP, Boudinot P. The antiviral innate immune response in fish: evolution and conservation of the IFN system. J Mol Biol. 2013;425(24):4904-20.
[53]
Xu L, Yang L, Liu W. Distinct evolution process among type I interferon in mammals. Protein Cell. 2013;4(5):383-92.
[54]
Marchalonis JJ, Whitfield GK, Schluter SF. Rapid evolutionary emergence of the combinatorial recognition repertoire. Integr Comp Biol. 2003;43(2):347-59.