Skip to main content
SpringerLink
Log in

The effect of transcription on enhancer activity in Drosophila melanogaster

  • Molecular Genetics
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

In higher eukaryotes, the level of gene transcription is under the control of DNA regulatory elements, such as promoter, from which transcription is initiated with the participation of RNA polymerase II and general transcription factors, as well as the enhancer, which increase the rate of transcription with the involvement of activator proteins and cofactors. It was demonstrated that enhancers are often located in the transcribed regions of the genome. We showed earlier that transcription negatively affected the activity of enhancers in Drosophila in model transgenic systems. In this study, we tested the effect of the distance between the leading promoter, enhancer, and target promoter on the inhibitory effect of transcription of different strength. It was demonstrated that the negative effect of transcription remained, but weakened with increased distance between the leading promoter and enhancer and with decreased distance between the enhancer and target promoter. Thus, transcription can modulate the activity of enhancers by controlling its maximum level.

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

Similar content being viewed by others

References

  1. Shlyueva, D., Stampfel, G., and Stark, A., Transcriptional enhancers: from properties to genome-wide predictions, Nat. Rev. Genet., 2014, vol. 15, pp. 272–286.

    Article  CAS  PubMed  Google Scholar 

  2. Bulger, M. and Groudine, M., Functional and mechanistic diversity of distal transcription enhancers, Cell, 2011, vol. 144, pp. 327–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Heintzman, N.D. and Ren, B., Finding distal regulatory elements in the human genome, Curr. Opin. Genet. Dev., 2009, vol. 19, pp. 541–549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chepelev, I., Wei, G., Wangsa, D., et al., Characterization of genome-wide enhancer–promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization, Cell Res., 2012, vol. 22, pp. 490–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Birnbaum, R.Y., Clowney, E.J., Agamy, O., et al., Coding exons function as tissue-specific enhancers of nearby genes, Genome Res., 2012, vol. 22, pp. 1059–1068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ritter, D.I., Dong, Z., Guo, S., and Chuang, J.H., Transcriptional enhancers in protein-coding exons of vertebrate developmental genes, PLoS One, 2012, vol. 7. e35202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bertone, P., Stolc, V., Royce, T.E., et al., Global identification of human transcribed sequences with genome tiling arrays, Science, 2004, vol. 306, pp. 2242–2246.

    Article  CAS  PubMed  Google Scholar 

  8. Kapranov, P., Cheng, J., Dike, S., et al., RNA maps reveal new RNA classes and a possible function for pervasive transcription, Science, 2007, vol. 316, pp. 1484–1488.

    Article  CAS  PubMed  Google Scholar 

  9. Cheng, J., Kapranov, P., Drenkow, J., et al., Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution, Science, 2005, vol. 308, pp. 1149–1154.

    Article  CAS  PubMed  Google Scholar 

  10. Young, R.S., Marques, A.C., Tibbit, C., et al., Identification and properties of 1119 candidate lincRNA loci in the Drosophila melanogaster genome, Genome Biol. Evol., 2012, vol. 4, pp. 427–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Birney, E., Stamatoyannopoulos, J.A., Dutta, A., et al., Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, Nature, 2007, vol. 447, pp. 799–816.

    Article  CAS  PubMed  Google Scholar 

  12. Wang, K. and Chang, H., Molecular mechanisms of long noncoding RNAs, Mol. Cell, 2011, vol. 43, pp. 904–914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hung, T., Wang, Y., Lin, M.F., et al., Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters, Nat. Genet., 2011, vol. 43, pp. 621–629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gummalla, M., Maeda, R.K., Castro Alvarez, J.J., et al., abd-A regulation by the iab-8 noncoding RNA, PLoS Genet., 2012, vol. 8. e1002720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Petruk, S., Sedkov, Y., Riley, K.M., et al., Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference, Cell, 2006, vol. 127, pp. 1209–1221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rinn, J.L., Kertesz, M., Wang, J.K., et al., Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs, Cell, 2007, vol. 129, pp. 1311–1323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhao, J., Sun, B.K., Erwin, J.A., et al., Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome, Science, 2008, vol. 322, pp. 750–756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pandey, R.R., Mondal, T., Mohammad, F., et al., Kcnq1ot1 antisense noncoding RNA mediates lineagespecific transcriptional silencing through chromatinlevel regulation, Mol. Cell, 2008, vol. 32, pp. 232–246.

    Article  CAS  PubMed  Google Scholar 

  19. Yang, P.K. and Kuroda, M.I., Noncoding RNAs and intranuclear positioning in monoallelic gene expression, Cell, 2007, vol. 128, pp. 777–786.

    Article  CAS  PubMed  Google Scholar 

  20. Kotake, Y., Nakagawa, T., Kitagawa, K., et al., Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene, Oncogene, 2011, vol. 30, pp. 1956–1962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yap, K.L., Li, S., Muñoz-Cabello, A.M., et al., Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a, Mol. Cell, 2010, vol. 38, pp. 662–674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schmitt, S., Prestel, M., and Paro, R., Intergenic transcription through a polycomb group response element counteracts silencing, Genes Dev., 2005, vol. 19, pp. 697–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ørom, U.A., Derrien, T. Beringer, M., et al., Long noncoding RNAs with enhancer-like function in human cells, Cell, 2010, vol. 143, pp. 46–58.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kim, T.K., Hemberg, M., Gray, J.M., et al., Widespread transcription at neuronal activity-regulated enhancers, Nature, 2010, vol. 465, pp. 182–187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. De Santa, F., Barozzi, I., Mietton, F., et al., A large fraction of extragenic RNA Pol II transcription sites overlap enhancers, PLoS Biol., 2010, vol. 8. e1000384

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kowalczyk, M.S., Hughes, J.R., Garrick, D., et al., Intragenic enhancers act as alternative promoters, Mol. Cell, 2012, vol. 45, pp. 447–458.

    Article  CAS  PubMed  Google Scholar 

  27. Bertani, S., Sauer, S., Bolotin, E., and Sauer, F., The noncoding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin, Mol. Cell, 2011, vol. 43, pp. 1040–1046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gomez, J.A., Wapinski, O.L., Yang, Y.W., et al., The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus, Cell, 2013, vol. 152, pp. 743–754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, K.C., Yang, Y.W., Liu, B., et al., A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression, Nature, 2011, vol. 472, pp. 120–124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lai, F., Orom, U.A., Cesaroni, M., et al., Activating RNAs associate with mediator to enhance chromatin architecture and transcription, Nature, 2013, vol. 494, pp. 497–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Spitale, R.C., Tsai, M.C., and Chang, H.Y., RNA templating the epigenome: long noncoding RNAs as molecular scaffolds, Epigenetics, 2011, vol. 6, pp. 539–543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Palmer, A.C., Egan, J.B., and Shearwin, K.E., Transcriptional interference by RNA polymerase pausing and dislodgement of transcription factors, Transcription, 2011, vol. 2, pp. 9–14.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mazo, A., Hodgson, J.W., Petruk, S., et al., Transcriptional interference: an unexpected layer of complexity in gene regulation, J. Cell Sci., 2007, vol. 120, pp. 2755–2761.

    Article  CAS  PubMed  Google Scholar 

  34. Martens, J.A., Laprade, L., and Winston, F., Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene, Nature, 2004, vol. 429, pp. 571–574.

    Article  CAS  PubMed  Google Scholar 

  35. Bird, A.J., Gordon, M., Eide, D.J., and Winge, D.R., Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts, EMBO J., 2006, vol. 25, pp. 5726–5734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lefevre, P., Witham, J., Lacroix, C.E., et al., The LPSinduced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription, Mol. Cell, 2008, vol. 32, pp. 129–139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Erokhin, M., Davydova, A., Parshikov, A., et al., Transcription through enhancers suppresses their activity in Drosophila, Epigenet. Chromatin, 2013, vol. 6, p. 31.

    Article  CAS  Google Scholar 

  38. Pirrotta, V., Vectors for P-mediated transformation in Drosophila, Biotechnology, 1988, vol. 10, pp. 437–456.

    CAS  PubMed  Google Scholar 

  39. Chetverina, D., Savitskaya, E., Maksimenko, O., et al., Red flag on the white reporter: a versatile insulator abuts the white gene in Drosophila and is omnipresent in mini-white constructs, Nucleic Acids Res., 2008, vol. 36, pp. 929–937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Savitskaya, E., Melnikova, L., Kostuchenko, M., et al., Study of long-distance functional interactions between Su(Hw) insulators that can regulate enhancer–promoter communication in Drosophila melanogaster, Mol. Cell Biol., 2006, vol. 26, pp. 754–761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Geyer, P.K. and Corces, V.G., Separate regulatory elements are responsible for the complex pattern of tissuespecific and developmental transcription of the yellow locus in Drosophila melanogaster, Genes Dev., 1987, vol. 1, pp. 996–1004.

    Article  CAS  PubMed  Google Scholar 

  42. Davydova, A.I., Erokhin, M.M., Georgiev, P.G., and Chetverina, D.A., Distant interactions between enhancers and promoters in Drosophila melanogaster are mediated by transgene-flanking Su(Hw) insulators, Russ. J. Genet., 2011, vol. 47, no. 8, pp. 917–922.

    Article  CAS  Google Scholar 

  43. Qian, S., Varjavand, B., and Pirrotta, V., Molecular analysis of the zeste-white interaction reveals a promoter-proximal element essential for distant enhancer–promoter communication, Genetics, 1992, vol. 131, pp. 79–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Brand, A.H. and Perrimon, N., Targeted gene expression as a means of altering cell fates and generating dominant phenotypes, Development, 1993, vol. 118, pp. 401–415.

    CAS  PubMed  Google Scholar 

  45. Golovnin, A., Birukova, I., Romanova, O., et al., An endogenous Su(Hw) insulator separates the yellow gene from the Achaete-scute gene complex in Drosophila, Development, 2003, vol. 130, pp. 3249–3258.

    Article  CAS  PubMed  Google Scholar 

  46. Karess, R.E. and Rubin, G.M., Analysis of P transposable element functions in Drosophila, Cell, 1984, vol. 38, pp. 135–146.

    Article  CAS  PubMed  Google Scholar 

  47. Rubin, G.M. and Spradling, A.C., Genetic transformation of Drosophila with transposable element vectors, Science, 1982, vol. 218, pp. 348–353.

    Article  CAS  PubMed  Google Scholar 

  48. Spradling, A.C. and Rubin, G.M., Transposition of cloned P elements into Drosophila germ line chromosomes, Science, 1982, vol. 218, pp. 341–347.

    Article  CAS  PubMed  Google Scholar 

  49. Martin, M., Meng, Y.B., and Chia, W., Regulatory elements involved in the tissue-specific expression of the yellow gene of Drosophila, Mol. Gen. Genet., 1989, vol. 218, pp. 118–126.

    Article  CAS  PubMed  Google Scholar 

  50. Heintzman, N.D., Hon, G.C., and Hawkins, R.D., Histone modifications at human enhancers reflect global cell-type-specific gene expression, Nature, 2009, vol. 459, pp. 108–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia

    M. M. Erokhin, A. I. Davydova, D. V. Lomaev, P. G. Georgiev & D. A. Chetverina

  2. LIA 1066, Laboratorie Franco-Russe de recherche en oncologie, Moscow, 119334, Russia

    M. M. Erokhin, A. I. Davydova, D. V. Lomaev, P. G. Georgiev & D. A. Chetverina

Authors
  1. M. M. Erokhin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. I. Davydova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. V. Lomaev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. G. Georgiev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. A. Chetverina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. M. Erokhin.

Additional information

Original Russian Text © M.M. Erokhin, A.I. Davydova, D.V. Lomaev, P.G. Georgiev, D.A. Chetverina, 2016, published in Genetika, 2016, Vol. 52, No. 1, pp. 37–46.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erokhin, M.M., Davydova, A.I., Lomaev, D.V. et al. The effect of transcription on enhancer activity in Drosophila melanogaster . Russ J Genet 52, 29–37 (2016). https://doi.org/10.1134/S1022795416010051

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795416010051

Keywords

Search

Navigation