Skip to main content
SpringerLink
Log in

Characterization and transcriptional regulation analysis of the porcine TNFAIP8L2 gene

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

Tumor necrosis factor alpha-induced protein 8-like 2 (TNFAIP8L2) is a new member of the tumor necrosis factor-α-induced protein 8 (TNFAIP8) family that functions as an important factor in the maintenance of immune homeostasis. In this study, we cloned the cDNA sequences and analyzed the genomic structure of porcine TNFAIP8L2. RH mapping using the IMpRH panel showed that this gene was closely linked to microsatellite marker SW512 in pig chromosome 4. Subcellular localization analysis showed GFP–TNFAIP8L2 fusion protein distributed in nucleus as well as cytoplasm including mitochondria and endoplasmic reticulum. Real-time PCR analysis revealed that porcine TNFAIP8L2 was more highly expressed in spleen than other tissues. To understand its characterization of transcriptional regulation, we cloned approximately 2 kb of 5′-regulatory region upstream to the porcine TNFAIP8L2 translational start site and generated sequential deletion constructs evaluated in dual-luciferase reporter assay. The results demonstrated that its core promoter is 435 base pairs (bp) upstream to the transcription initiation site. Then, site-directed mutation experiment combined with electrophoretic mobility shift assay (EMSA) indicated that M-CAT binding factor (MCBF) and activator protein 1 (AP-1) were important transcription factors for porcine TNFAIP8L2. These findings provide an important basis for further understanding of porcine TNFAIP8L2 regulation and function in swine.

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. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Aihara Y, Kurabayashi M, Saito Y, Ohyama Y, Tanaka T, Takeda S, Tomaru K, Sekiguchi K, Arai M, Nakamura T, Nagai R (2000) Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of m-cat element within the promoter. Hypertension 36(1):48–53

    CAS  PubMed  Google Scholar 

  • Andersson-Eklund L, Marklund L, Lundstrom K, Haley CS, Andersson K, Hansson I, Moller M, Andersson L (1998) Mapping quantitative trait loci for carcass and meat quality traits in a wild boar × large white intercross. J Anim Sci 76(3):694–700

    CAS  PubMed  Google Scholar 

  • Angel P, Karin M (1991) The role of jun, fos and the ap-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072(2–3):129–157

    CAS  PubMed  Google Scholar 

  • Chow G, Knudson W (2005) Characterization of promoter elements of the human hyal-2 gene. J Biol Chem 280(29):26904–26912

    Article  CAS  PubMed  Google Scholar 

  • Eferl R, Wagner EF (2003) Ap-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3(11):859–868

    Article  CAS  PubMed  Google Scholar 

  • Fabre-Suver C, Hauschka SD (1996) A novel site in the muscle creatine kinase enhancer is required for expression in skeletal but not cardiac muscle. J Biol Chem 271(9):4646–4652

    Article  CAS  PubMed  Google Scholar 

  • Farrance IK, Mar JH, Ordahl CP (1992) M-cat binding factor is related to the sv40 enhancer binding factor, tef-1. J Biol Chem 267(24):17234–17240

    CAS  PubMed  Google Scholar 

  • Freundt EC, Bidere N, Lenardo MJ (2008) A different tipe of immune homeostasis. Cell 133(3):401–402

    Article  CAS  PubMed  Google Scholar 

  • Genini S, Delputte PL, Malinverni R, Cecere M, Stella A, Nauwynck HJ, Giuffra E (2008) Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus. J Gen Virol 89(Pt 10):2550–2564

    Article  CAS  PubMed  Google Scholar 

  • Hiraiwa H, Sawazaki T, Suzuki K, Fujishima-Kanaya N, Toki D, Ito Y, Uenishi H, Hayashi T, Awata T, Yasue H (2003) Elucidation of correspondence between swine chromosome 4 and human chromosome 1 by assigning 27 genes to the imprh map, and development of microsatellites in the proximity of 14 genes. Cytogenet Genome Res 101(1):84–89

    Article  CAS  PubMed  Google Scholar 

  • Humbert O, Achour I, Lautier D, Laurent G, Salles B (2003) Hmsh2 expression is driven by ap1-dependent regulation through phorbol-ester exposure. Nucleic Acids Res 31(19):5627–5634

    Article  CAS  PubMed  Google Scholar 

  • Jalava A, Mai S (1994) Fos and jun form cell specific protein complexes at the neuropeptide tyrosine promoter. Oncogene 9(8):2369–2375

    CAS  PubMed  Google Scholar 

  • Karin M, Liu Z, Zandi E (1997) Ap-1 function and regulation. Curr Opin Cell Biol 9(2):240–246

    Article  CAS  PubMed  Google Scholar 

  • Kumar D, Whiteside TL, Kasid U (2000) Identification of a novel tumor necrosis factor-alpha-inducible gene, scc-s2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein. J Biol Chem 275(4):2973–2978

    Article  CAS  PubMed  Google Scholar 

  • Kumar D, Gokhale P, Broustas C, Chakravarty D, Ahmad I, Kasid U (2004) Expression of scc-s2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of mda-mb 435 cells. Oncogene 23(2):612–616

    Article  CAS  PubMed  Google Scholar 

  • Li D, Song L, Fan Y, Li X, Li Y, Chen J, Zhu F, Guo C, Shi Y, Zhang L (2009) Down-regulation of tipe2 mrna expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Immunol 133:422–427

    Article  CAS  PubMed  Google Scholar 

  • Mar JH, Ordahl CP (1990) M-cat binding factor, a novel trans-acting factor governing muscle-specific transcription. Mol Cell Biol 10(8):4271–4283

    CAS  PubMed  Google Scholar 

  • Marklund L, Nystrom PE, Stern S, Andersson-Eklund L, Andersson L (1999) Confirmed quantitative trait loci for fatness and growth on pig chromosome 4. Heredity 82(Pt 2):134–141

    Article  PubMed  Google Scholar 

  • McWhinney C, Robishaw JD (2008) Myocyte-specific m-cat and mef-1 elements regulate g-protein gamma 3 gene (gamma3) expression in cardiac myocytes. DNA Cell Biol 27(7):367–376

    Article  CAS  PubMed  Google Scholar 

  • Milan D, Hawken R, Cabau C, Leroux S, Genet C, Lahbib Y, Tosser G, Robic A, Hatey F, Alexander L, Beattie C, Schook L, Yerle M, Gellin J (2000) Imprh server: an rh mapping server available on the web. Bioinformatics 16(6):558–559

    Article  CAS  PubMed  Google Scholar 

  • Patel S, Wang FH, Whiteside TL, Kasid U (1997) Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response. Oral Oncol 33(3):197–203

    Article  CAS  PubMed  Google Scholar 

  • Sun H, Gong S, Carmody RJ, Hilliard A, Li L, Sun J, Kong L, Xu L, Hilliard B, Hu S, Shen H, Yang X, Chen YH (2008) Type2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell 133(3):415–426

    Article  CAS  PubMed  Google Scholar 

  • Tu SP, Chi AL, Ai W, Takaishi S, Dubeykovskaya Z, Quante M, Fox JG, Wang TC (2009) P53 inhibition of ap1-dependent tff2 expression induces apoptosis and inhibits cell migration in gastric cancer cells. Am J Physiol 297(2):G385–G396

    CAS  Google Scholar 

  • Valmiki MG, Ramos JW (2009) Death effector domain-containing proteins. Cell Mol Life Sci 66(5):814–830

    Article  CAS  PubMed  Google Scholar 

  • Walling GA, Archibald AL, Cattermole JA, Downing AC, Finlayson HA, Nicholson D, Visscher PM, Walker CA, Haley CS (1998) Mapping of quantitative trait loci on porcine chromosome 4. Anim Genet 29(6):415–424

    Article  CAS  PubMed  Google Scholar 

  • Walling GA, Visscher PM, Andersson L, Rothschild MF, Wang L, Moser G, Groenen MA, Bidanel JP, Cepica S, Archibald AL, Geldermann H, de Koning DJ, Milan D, Haley CS (2000) Combined analyses of data from quantitative trait loci mapping studies. Chromosome 4 effects on porcine growth and fatness. Genetics 155(3):1369–1378

    CAS  PubMed  Google Scholar 

  • Woodward MJ, de Boer J, Heidorn S, Hubank M, Kioussis D, Williams O, Brady HJ (2009) Tnfaip8 is an essential gene for the regulation of glucocorticoid-mediated apoptosis of thymocytes. Cell Death Differ 17:316–323

    Article  PubMed  Google Scholar 

  • Yerle M, Pinton P, Robic A, Alfonso A, Palvadeau Y, Delcros C, Hawken R, Alexander L, Beattie C, Schook L, Milan D, Gellin J (1998) Construction of a whole-genome radiation hybrid panel for high-resolution gene mapping in pigs. Cytogenet Cell Genet 82(3–4):182–188

    Article  CAS  PubMed  Google Scholar 

  • You Z, Ouyang H, Lopatin D, Polver PJ, Wang CY (2001) Nuclear factor-kappa b-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity. J Biol Chem 276(28):26398–26404

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Chakravarty D, Sakabe I, Mewani RR, Boudreau HE, Kumar D, Ahmad I, Kasid UN (2006) Role of scc-s2 in experimental metastasis and modulation of vegfr-2, mmp-1, and mmp-9 expression. Mol Ther 13(5):947–955

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Wang J, Fan C, Li H, Sun H, Gong S, Chen YH, Shi Y (2009) Crystal structure of tipe2 provides insights into immune homeostasis. Nat Struct Mol Biol 16(1):89–90

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This research was funded by National Natural Science Foundation of China (Grant No. U0731003) and National Key Basic Research Plan (973 Project) (Grant No. 2006CB102101).

Author information

Authors and Affiliations

  1. State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen University, Guangzhou, 510006, People’s Republic of China

    Anning Li, Yaosheng Chen, Xiao Zhao, Yuna Niu, Peiqing Cong, Zongwu Zhang, Weiquan Chen, Wei Jiang & Delin Mo

Authors
  1. Anning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yaosheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuna Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peiqing Cong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zongwu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weiquan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Delin Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Delin Mo.

Additional information

Communicated by L. Andersson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, A., Chen, Y., Zhao, X. et al. Characterization and transcriptional regulation analysis of the porcine TNFAIP8L2 gene. Mol Genet Genomics 284, 185–195 (2010). https://doi.org/10.1007/s00438-010-0558-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-010-0558-z

Keywords

Search

Navigation