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Transcriptional variations mediated by an alternative promoter of the FPR3 gene

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Abstract

Formyl peptide receptor 3 (FPR3) is a potential player in innate immunity and appears with FPR2 as a FPR cluster during primate evolution. Comparative genome analyses indicate that a segmental duplication (SD) event upstream of the FPR3 gene after the divergence of New and Old World monkeys led to the emergence of an alternative promoter. In this study we combined computational and experimental approaches to identify a FPR3 gene that is controlled by an alternative promoter derived during a SD event. Its transcriptional activity was detected by quantitative reverse transcription polymerase chain reaction. Human alternative transcripts (FPR3-1 and FPR3-2) showed tissue-specific patterns with strong expressions in lung or uterus, while the FPR3-1 transcript of rhesus macaque is broadly expressed in various tissues. Overall, transcriptional variations of FPR3 occur by an alternative promoter during primate evolution.

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References

  • Ahn K, Huh JW, Park SJ, Kim DS, Ha HS et al (2008) Selection of internal reference genes for SYBR green qRT-PCR studies of rhesus monkey (Macaca mulatta) tissues. BMC Mol Biol 9:78

    Article  PubMed  Google Scholar 

  • Akam M (1998) Hox genes, homeosis and the evolution of segment identity: no need for hopeless monsters. Int J Dev Biol 42:445–451

    PubMed  CAS  Google Scholar 

  • Alvarez V, Coto E, Setién F, González-Roces S, López-Larrea C (1996) Molecular evolution of the N-formyl peptide and C5a receptors in non-human primates. Immunogenetics 44:446–452

    Article  PubMed  CAS  Google Scholar 

  • Bailey JA, Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 7:552–564

    Article  PubMed  CAS  Google Scholar 

  • Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV et al (2002) Recent segmental duplications in the human genome. Science 297:1003–1007

    Article  PubMed  CAS  Google Scholar 

  • Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C (1992) Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics 13:437–440

    Article  PubMed  CAS  Google Scholar 

  • Blekhman R, Oshlack A, Gilad Y (2009) Segmental duplications contribute to gene expression differences between humans and chimpanzees. Genetics 182:627–630

    Article  PubMed  Google Scholar 

  • Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K et al (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38:626–635

    Article  PubMed  CAS  Google Scholar 

  • Cohen CJ, Lock WM, Mager DL (2009) Endogenous retroviral LTRs as promoters for human genes: a critical assessment. Gene 448:105–114

    Article  PubMed  CAS  Google Scholar 

  • Elagoz A, Henderson D, Babu PS, Salter S, Grahames C et al (2004) A truncated form of CKbeta8–1 is a potent agonist for human formyl peptide-receptor-like 1 receptor. Br J Pharmacol 141:37–46

    Article  PubMed  CAS  Google Scholar 

  • Flagel LE, Wendel JF (2009) Gene duplication and evolutionary novelty in plants. New Phytol 183:557–564

    Article  PubMed  Google Scholar 

  • Frazer KA, Chen X, Hinds DA, Pant PV, Patil N et al (2003) Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates. Genome Res 13:341–346

    Article  PubMed  CAS  Google Scholar 

  • Gao JL, Chen H, Filie JD, Kozak CA, Murphy PM (1998) Differential expansion of the N-formyl peptide receptor gene cluster in human and mouse. Genomics 51:270–276

    Article  PubMed  CAS  Google Scholar 

  • Harada M, Habata Y, Hosoya M, Nishi K, Fujii R et al (2004) N-formylated humanin activates both formyl peptide receptor-Like 1 and 2. Biochem Biophys Res Commun 324:255–261

    Article  PubMed  CAS  Google Scholar 

  • Haviland DL, Borel AC, Fleischer DT, Haviland JC, Wetsel RA (1993) Structure, 5′-flanking sequence, and chromosome location of the human N-formyl peptide receptor gene. A single-copy gene comprised of two exons on chromosome 19q.13.3 that yields two distinct transcripts by alternative polyadenylation. Biochemistry 32:4168–4174

    Article  PubMed  CAS  Google Scholar 

  • Hughes TA (2006) Regulation of gene expression by alternative untranslated regions. Trends Genet 22:119–122

    Article  PubMed  CAS  Google Scholar 

  • Hughes JF, Coffin JM (2001) Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29:487–489

    Article  PubMed  CAS  Google Scholar 

  • Hughes JF, Coffin JM (2005) Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics 171:1183–1194

    Article  PubMed  CAS  Google Scholar 

  • Hwang SB (1990) Specific receptors of platelet-activation factor, receptor heterogeneity, and signal transduction mechanisms. J Lipid Med 2:123–158

    CAS  Google Scholar 

  • International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  Google Scholar 

  • Jurka J, Milosavljevic A (1991) Reconstruction and analysis of human Alu genes. J Mol Evol 32:105–121

    Article  PubMed  CAS  Google Scholar 

  • Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T et al (2006) Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome Res 16:55–65

    Article  PubMed  CAS  Google Scholar 

  • Koszul R, Caburet S, Dujon B, Fischer G (2004) Eucaryotic genome evolution through the spontaneous duplication of large chromosomal segments. EMBO J 23:234–243

    Article  PubMed  CAS  Google Scholar 

  • Landry JR, Mager DL, Wilhelm BT (2003) Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet 19:640–648

    Article  PubMed  CAS  Google Scholar 

  • Le Y, Oppenheim JJ, Wang JM (2001) Pleiotropic roles of formyl peptide receptors. Cytokine Growth Factor Rev 12:91–105

    Article  PubMed  CAS  Google Scholar 

  • Liberles SD, Horowitz LF, Kuang D, Contos JJ, Wilson KL et al (2009) Formyl peptide receptors are candidate chemosensory receptors in the vomeronasal organ. Proc Natl Acad Sci USA 106:9842–9847

    Article  PubMed  CAS  Google Scholar 

  • Maldonado-Pérez D, Golightly E, Denison FC, Jabbour HN, Norman JE (2011) A role for lipoxin A4 as anti-inflammatory and proresolution mediator in human parturition. FASEB J 25:569–575

    Article  PubMed  Google Scholar 

  • Migeotte I, Communi D, Parmentier M (2006) Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev 17:501–519

    Article  PubMed  CAS  Google Scholar 

  • Murnane JP (2006) Telomeres and chromosome instability. DNA Repair (Amst) 5:1082–1092

    Article  CAS  Google Scholar 

  • Newman TL, Tuzun E, Morrison VA, Hayden KE, Ventura M et al (2005) A genome-wide survey of structural variation between human and chimpanzee. Genome Res 15:1344–1356

    Article  PubMed  CAS  Google Scholar 

  • Pâques F, Haber JE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63:349–404

    PubMed  Google Scholar 

  • Rhesus Macaque Genome Sequencing Analysis Consortium (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222–234

    Article  Google Scholar 

  • Riboldi E, Musso T, Moroni E, Urbinati C, Bernasconi S et al (2005) Cutting edge: proangiogenic properties of alternatively activated dendritic cells. J Immunol 175:2788–2792

    PubMed  CAS  Google Scholar 

  • Sequencing Chimpanzee, Consortium Analysis (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437:69–87

    Article  Google Scholar 

  • Sharp AJ, Cheng Z, Eichler EE (2006) Structural variation of the human genome. Annu Rev Genomics Hum Genet 7:407–442

    Article  PubMed  CAS  Google Scholar 

  • She X, Liu G, Ventura M, Zhao S, Misceo D et al (2006) A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications. Genome Res 16:576–583

    Article  PubMed  CAS  Google Scholar 

  • Smith GP (1976) Evolution of repeated DNA sequences by unequal crossover. Science 191:528–535

    Article  PubMed  CAS  Google Scholar 

  • Snyderman R, Uhing RJ (1992) Chemoattractant stimulus-response coupling. In: Gallin JI, Goldstein IM, Snyderman R (eds) Inflammation: Basic Principles and Clinical Correlates. Lippincott Williams & Wilkins, Philadelphia, pp 421–439

    Google Scholar 

  • Stankiewicz P, Lupski JR (2002) Genome architecture, rearrangements and genomic disorders. Trends Genet 18:74–82

    Article  PubMed  CAS  Google Scholar 

  • Stern DL (1998) A role of Ultrabithorax in morphological differences between Drosophila species. Nature 396:463–466

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  • Tsuritani K, Irie T, Yamashita R, Sakakibara Y, Wakaguri H et al (2007) Distinct class of putative “non-conserved” promoters in humans: comparative studies of alternative promoters of human and mouse genes. Genome Res 17:1005–1014

    Article  PubMed  CAS  Google Scholar 

  • Van Compernolle SE, Clark KL, Rummel KA, Todd SC (2003) Expression and function of formyl peptide receptors on human fibroblast cells. J Immunol 171:2050–2056

    Google Scholar 

  • Wang ZG, Ye RD (2002) Characterization of two new members of the formyl peptide receptor gene family from 129S6 mice. Gene 299:57–63

    Article  PubMed  CAS  Google Scholar 

  • Wilson MD, Cheung J, Martindale DW, Scherer SW, Koop BF (2006) Comparative analysis of the paired immunoglobulin-like receptor (PILR) locus in six mammalian genomes: duplication, conversion, and the birth of new genes. Physiol Genomics 27:201–218

    Article  PubMed  CAS  Google Scholar 

  • Wu C, Orozco C, Boyer J, Leglise M, Goodale J et al (2009) BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10:R130

    Article  PubMed  Google Scholar 

  • Yang D, Chen Q, Gertz B, He R, Phulsuksombati M, Ye RD, Oppenheim JJ (2002) Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation. J Leukoc Biol 72:598–607

    PubMed  CAS  Google Scholar 

  • Yang EM, Kim SH, Kim NH, Park HS (2010) The genetic association of the FPRL1 promoter polymorphism with chronic urticaria in a Korean population. Ann Allergy Asthma Immunol 105:96–97

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jungnam Lee and Nicholas Meyerson for comments on the manuscript. This study was financially supported by Pusan National University in program Post-Doc 2010.

Accession numbers

AB500093: Callithrix jacchus DNA, MER21C element including AluSx, complete sequence.

AB500092: Ateles geoffroyi DNA, LTR 54 element, complete sequence.

AB500091: Aotus trivirgatus DNA, LTR 54 element, complete sequence.

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Authors and Affiliations

  1. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea

    Hong-Seok Ha, Jeong-An Gim & Heui-Soo Kim

  2. National Primate Research Center, KRIBB, Ochang, Chungbuk, 363-883, Republic of Korea

    Jae-Won Huh

  3. Department of Nanobiomedical Science & WCU Research Center, Dankook University, Cheonan, 330-714, Republic of Korea

    Kyudong Han

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  1. Hong-Seok Ha
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Corresponding author

Correspondence to Heui-Soo Kim.

Electronic supplementary material

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335_2011_9341_MOESM1_ESM.tif

Supplementary material 1: Phylogenetic tree of LTR54 related FPR3 gene in various primates. The DR-LTR54 and OR-LTR54 families were completely separated into DR and OR groups, and single LTR54 clustered with the OR group. The black boxes indicate DR-LTR54 in various primates, and the white boxes indicate OR-LTR54 in various primates. The white circles show single LTR54 in New World monkeys. As an out group, paralogous LTR54 randomly selected in human genome was used (TIFF 111 kb)

335_2011_9341_MOESM2_ESM.tif

Supplementary material 2: Comparison of expression patterns among FPR family. Expression data was previously reported by Gao et al. 1998; Wang et al. 2002; Elagoz et al. 2004; Harada et al. 2004; Riboldi et al. 2005 (direct real-time PCR data, transformed RT-PCR and Northern data through ImageJ program) (TIFF 142 kb)

335_2011_9341_MOESM3_ESM.tif

Supplementary material 3: Quantitative analyses of human FPR2-1 transcripts. Graphs indicate expression of human FPR2-1 in various tissue panels. Each column represents the mean value with a standard error in triplicate determinations (TIFF 99 kb)

335_2011_9341_MOESM4_ESM.tif

Supplementary material 4: Quantitative analyses of FPR3-1 and FPR3-2 transcripts in A549 and HeLa cells. Graphs show expression pattern of (a) human FPR3-1, (b) human FPR3-2, in A549 and HeLa cells. Notably, the human FPR3-2 was not expressed in A549 cells. Each column represents the mean value with a standard error in triplicate determinations (TIFF 75 kb)

335_2011_9341_MOESM5_ESM.tif

Supplementary material 5: Conservation of FPR3 gene. Analysis of conservation by Phylop (a) and Phastcons (b) of UCSC genome browser and VISTA browser (c) (TIFF 426 kb)

335_2011_9341_MOESM6_ESM.tif

Supplementary material 6: Analysis of histone modification status. (a) Histone modification status of SR within human FPR2 gene (b) Histone modification status of DR and OR within human FPR3 gene. Boxes indicate SR, DR, and OR (TIFF 394 kb)

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Ha, HS., Huh, JW., Gim, JA. et al. Transcriptional variations mediated by an alternative promoter of the FPR3 gene. Mamm Genome 22, 621–633 (2011). https://doi.org/10.1007/s00335-011-9341-7

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