Enhancers increase the probability but not the level of gene expression - PubMed (original) (raw)

Enhancers increase the probability but not the level of gene expression

M C Walters et al. Proc Natl Acad Sci U S A. 1995.

Abstract

We have studied enhancer function in transient and stable expression assays in mammalian cells by using systems that distinguish expressing from nonexpressing cells. When expression is studied in this way, enhancers are found to increase the probability of a construct being active but not the level of expression per template. In stably integrated constructs, large differences in expression level are observed but these are not related to the presence of an enhancer. Together with earlier studies, these results suggest that enhancers act to affect a binary (on/off) switch in transcriptional activity. Although this idea challenges the widely accepted model of enhancer activity, it is consistent with much, if not all, experimental evidence on this subject. We hypothesize that enhancers act to increase the probability of forming a stably active template. When randomly integrated into the genome, enhancers may affect a metastable state of repression/activity, permitting expression in regions that would not permit activity of an isolated promoter.

PubMed Disclaimer

Similar articles

• Immunoglobulin kappa gene enhancers synergistically activate gene expression but independently determine chromatin structure.
  Blasquez VC, Hale MA, Trevorrow KW, Garrard WT. Blasquez VC, et al. J Biol Chem. 1992 Nov 25;267(33):23888-93. J Biol Chem. 1992. PMID: 1429727
• A reporter system using a flow cytometer to detect promoter/enhancer activity in lymphoid cell lines.
  Mazda O, Teshigawara K, Fujimoto S, Hattori N, Dou YM, Katsura Y. Mazda O, et al. J Immunol Methods. 1994 Feb 28;169(1):53-61. doi: 10.1016/0022-1759(94)90124-4. J Immunol Methods. 1994. PMID: 8133073
• In trans promoter activation by enhancers in transient transfection.
  Smirnov NA, Akopov SB, Didych DA, Nikolaev LG. Smirnov NA, et al. Gene. 2017 Mar 1;603:15-20. doi: 10.1016/j.gene.2016.12.005. Epub 2016 Dec 9. Gene. 2017. PMID: 27956170
• Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers.
  Kim TK, Hemberg M, Gray JM. Kim TK, et al. Cold Spring Harb Perspect Biol. 2015 Jan 5;7(1):a018622. doi: 10.1101/cshperspect.a018622. Cold Spring Harb Perspect Biol. 2015. PMID: 25561718 Free PMC article. Review.
• Transcriptional enhancers can act in trans.
  Müller HP, Schaffner W. Müller HP, et al. Trends Genet. 1990 Sep;6(9):300-4. doi: 10.1016/0168-9525(90)90236-y. Trends Genet. 1990. PMID: 2238088 Review.

Cited by

• Slow, stochastic transgene repression with properties of a timer.
  Wang CL, Yang DC, Wabl M. Wang CL, et al. Genome Biol. 2006;7(6):R47. doi: 10.1186/gb-2006-7-6-r47. Genome Biol. 2006. PMID: 16764729 Free PMC article.
• Gene silencing dynamics are modulated by transiently active regulatory elements.
  Vermunt MW, Luan J, Zhang Z, Thrasher AJ, Huang A, Saari MS, Khandros E, Beagrie RA, Zhang S, Vemulamada P, Brilleman M, Lee K, Yano JA, Giardine BM, Keller CA, Hardison RC, Blobel GA. Vermunt MW, et al. Mol Cell. 2023 Mar 2;83(5):715-730.e6. doi: 10.1016/j.molcel.2023.02.006. Mol Cell. 2023. PMID: 36868189 Free PMC article.
• Memories of lost enhancers.
  Sen R, Grosschedl R. Sen R, et al. Genes Dev. 2010 May 15;24(10):973-9. doi: 10.1101/gad.1930610. Genes Dev. 2010. PMID: 20478992 Free PMC article.
• A theoretical model for the regulation of Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila melanogaster.
  Louis M, Holm L, Sánchez L, Kaufman M. Louis M, et al. Genetics. 2003 Nov;165(3):1355-84. doi: 10.1093/genetics/165.3.1355. Genetics. 2003. PMID: 14668388 Free PMC article.
• Single-Cell Isolation and Gene Analysis: Pitfalls and Possibilities.
  Hodne K, Weltzien FA. Hodne K, et al. Int J Mol Sci. 2015 Nov 10;16(11):26832-49. doi: 10.3390/ijms161125996. Int J Mol Sci. 2015. PMID: 26569222 Free PMC article. Review.

References

1. 1. Biochemistry. 1979 Dec 11;18(25):5726-31 - PubMed
2. 1. J Exp Med. 1994 Oct 1;180(4):1251-62 - PubMed
3. 1. Nucleic Acids Res. 1981 Nov 25;9(22):6047-68 - PubMed
4. 1. Cell. 1981 Dec;27(2 Pt 1):299-308 - PubMed
5. 1. J Mol Biol. 1982 Apr 15;156(3):549-65 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central