Skip to main content
SpringerLink
Log in

Transcriptional directionality of the human insulin-degrading enzyme promoter

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Unidirectional promoters dominate among mammalian genomes. However, the mechanism through which the transcriptional directionality of promoters is accomplished remains to be clarified. Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc metalloprotease, whose promoter contains a CpG island. We previously showed that the basal promoter region of mouse IDE has bidirectional transcriptional activity, but an upstream promoter element blocks its antisense transcription. Therefore, we wonder whether the human IDE promoter contains an analogous element. Similarly, the basal promoter region of human IDE (−102 ~ +173 and −196 ~ +173 relative to the transcription start site) showed bidirectional transcriptional activity. However, the region from −348 to +173 could only be transcribed from the normal orientation, implying that an upstream promoter element between −348 and −196 blocks the antisense transcription of the human IDE promoter. Through promoter deletion and mutagenesis analysis, we mapped this element precisely and found that the upstream promoter element locates between −318 and −304. Furthermore, the transcription-blocking elements in the mouse and human IDE promoters inhibited the transcription of the SV40 promoter when put downstream of it. In conclusion, we identify an upstream promoter element which blocks the antisense transcription of the human IDE promoter. Our studies are helpful to clarify the transcriptional directionality of promoters.

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

Similar content being viewed by others

References

  1. Adachi N, Lieber MR (2002) Bidirectional gene organization: a common architectural feature of the human genome. Cell 109(7):807–809

    Article  PubMed  CAS  Google Scholar 

  2. Trinklein ND, Aldred SF, Hartman SJ, Schroeder DI, Otillar RP, Myers RM (2004) An abundance of bidirectional promoters in the human genome. Genome Res 14(1):62–66. doi:10.1101/gr.1982804

    Article  PubMed  CAS  Google Scholar 

  3. Liao WC, Ash J, Johnson LF (1994) Bidirectional promoter of the mouse thymidylate synthase gene. Nucleic Acids Res 22(20):4044–4049

    Article  PubMed  CAS  Google Scholar 

  4. Qvist H, Sjostrom H, Noren O (1998) The TATA-less, GC-rich porcine dipeptidylpeptidase IV (DPPIV) promoter shows bidirectional activity. Biol Chem 379(1):75–81

    PubMed  CAS  Google Scholar 

  5. Dong S, Lester L, Johnson LF (2000) Transcriptional control elements and complex initiation pattern of the TATA-less bidirectional human thymidylate synthase promoter. J Cell Biochem 77(1):50–64

    Article  PubMed  CAS  Google Scholar 

  6. Kawai Y, Asai K, Miura Y, Inoue Y, Yamamoto M, Moriyama A, Yamamoto N, Kato T (2003) Structure and promoter activity of the human glia maturation factor-gamma gene: a TATA-less, GC-rich and bidirectional promoter. Biochim Biophys Acta 1625(3):246–252

    Article  PubMed  CAS  Google Scholar 

  7. Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engstrom PG, Frith MC, Forrest AR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F, Suzuki H, Grimmond SM, Wells CA, Orlando V, Wahlestedt C, Liu ET, Harbers M, Kawai J, Bajic VB, Hume DA, Hayashizaki Y (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38(6):626–635. doi:10.1038/ng1789

    Article  PubMed  CAS  Google Scholar 

  8. Lin JM, Collins PJ, Trinklein ND, Fu Y, Xi H, Myers RM, Weng Z (2007) Transcription factor binding and modified histones in human bidirectional promoters. Genome Res 17(6):818–827. doi:10.1101/gr.5623407

    Article  PubMed  CAS  Google Scholar 

  9. Churchman LS, Weissman JS (2011) Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469(7330):368–373. doi:10.1038/nature09652

    Article  PubMed  CAS  Google Scholar 

  10. Tan-Wong SM, Zaugg JB, Camblong J, Xu Z, Zhang DW, Mischo HE, Ansari AZ, Luscombe NM, Steinmetz LM, Proudfoot NJ (2012) Gene loops enhance transcriptional directionality. Science 338(6107):671–675. doi:10.1126/science.1224350

    Article  PubMed  CAS  Google Scholar 

  11. Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322(5909):1845–1848. doi:10.1126/science.1162228

    Article  PubMed  CAS  Google Scholar 

  12. Seila AC, Calabrese JM, Levine SS, Yeo GW, Rahl PB, Flynn RA, Young RA, Sharp PA (2008) Divergent transcription from active promoters. Science 322(5909):1849–1851. doi:10.1126/science.1162253

    Article  PubMed  CAS  Google Scholar 

  13. Authier F, Posner BI, Bergeron JJ (1996) Insulin-degrading enzyme. Clin Invest Med 19(3):149–160

    PubMed  CAS  Google Scholar 

  14. Zhang L, Ding Q, Wang Z (2012) Nuclear respiratory factor 1 mediates the transcription initiation of insulin-degrading enzyme in a tata box-binding protein-independent manner. PLoS ONE 7(8):e42035. doi:10.1371/journal.pone.0042035

    Article  PubMed  CAS  Google Scholar 

  15. Zhang L, Ding Q, Wang P, Wang Z (2013) An upstream promoter element blocks the reverse transcription of the mouse insulin-degrading enzyme gene. Biochem Biophys Res Commun 430(1):26–31. doi:10.1016/j.bbrc.2012.11.052

    Article  PubMed  CAS  Google Scholar 

  16. Yang MQ, Elnitski LL (2008) Diversity of core promoter elements comprising human bidirectional promoters. BMC Genomics 9(Suppl 2):S3. doi:10.1186/1471-2164-9-S2-S3

    Article  Google Scholar 

  17. Zanotto E, Shah ZH, Jacobs HT (2007) The bidirectional promoter of two genes for the mitochondrial translational apparatus in mouse is regulated by an array of CCAAT boxes interacting with the transcription factor NF-Y. Nucleic Acids Res 35(2):664–677. doi:10.1093/nar/gkl1037

    Article  PubMed  CAS  Google Scholar 

  18. Zanotto E, Hakkinen A, Teku G, Shen B, Ribeiro AS, Jacobs HT (2009) NF-Y influences directionality of transcription from the bidirectional Mrps12/Sarsm promoter in both mouse and human cells. Biochim Biophys Acta 1789(5):432–442. doi:10.1016/j.bbagrm.2009.05.001

    Article  PubMed  CAS  Google Scholar 

  19. Tiana M, Villar D, Perez-Guijarro E, Gomez-Maldonado L, Molto E, Fernandez-Minan A, Gomez-Skarmeta JL, Montoliu L, del Peso L (2012) A role for insulator elements in the regulation of gene expression response to hypoxia. Nucleic Acids Res 40(5):1916–1927. doi:10.1093/nar/gkr842

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Basic Research Program (973 Project) of China (No. 2013CB530802), and the Tsinghua University Initiative Scientific Research Program (20111081143).

Author information

Authors and Affiliations

  1. MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing, 100084, China

    Lang Zhang, Pan Wang, Qingyang Ding & Zhao Wang

Authors
  1. Lang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qingyang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao Wang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 33 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Wang, P., Ding, Q. et al. Transcriptional directionality of the human insulin-degrading enzyme promoter. Mol Cell Biochem 382, 237–242 (2013). https://doi.org/10.1007/s11010-013-1739-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1739-y

Keywords

Search

Navigation