Negative Regulatory Elements (NREs)


Negative regulatory elements (NREs) are deoxyribonucleic acid (DNA) sequences that repress gene expression. NREs can act locally to repress expression of individual genes, or globally to repress expression of an expansive chromosomal domain. In either case, NREs act as binding sites for specific proteins, which in turn interact with other factors either to block recruitment of ribonucleic acid (RNA) polymerase or to facilitate formation of heterochromatin.

Keywords: chromatin; repression; silencing; transcription

Figure 1.

Schematic summary of a eukaryotic RNAP II promoter. Repressor and activator proteins are depicted as bipartite structures: one domain binds the cognate DNA sequence, either the NRE (URS) or positive regulatory element (UAS or enhancer), and the other domain interacts with components of the transcription machinery. Some repressors and activators interact directly with the core transcriptional machinery, including the general transcription factors (GTFs) or RNAP II itself, whereas others exert their effects through corepressor or coactivator complexes. These cofactors can in turn interact with the core machinery, as depicted here, or affect chromatin structure (Malave and Dent, ). The relative position of the URS and UAS elements depicted here is arbitrary.

Figure 2.

Schematic summary of the structure of SIR‐mediated silent DNA. Like URS elements, silencers function as binding sites for sequence‐specific DNA‐binding proteins (a, b, c), which in turn bind SIR proteins to turn off gene expression. In contrast to NREs that repress local gene expression, silencers repress an expansive chromosomal domain. The silencer serves as a nucleation site for spreading the SIR complex along adjacent nucleosomes (N) (Rusche et al., ). This structure is comparable to the heterochromatin of higher eukaryotes.



Jacob F and Monod J (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3: 318–356.

Malave TM and Dent SY (2006) Transcriptional repression by Tup1–Ssn6. Biochemistry & Cell Biology 84: 437–443.

Maldonado E, Hampsey M and Reinberg D (1999) Repression: targeting the heart of the matter. Cell 99: 455–458.

Mathias JR, Hanlon SE, O’Flanagan RA, Sengupta AM and Vershon AK (2004) Repression of the yeast HO gene by the MATα2 and MATa1 homeodomain proteins. Nucleic Acids Research 32: 6469–6478.

Nair SK and Burley SK (2006) Structural aspects of interactions within the Myc/Max/Mad network. Current Topics in Microbiology & Immunology 302: 123–143.

Pierce M, Benjamin KR, Montano SP et al. (2003) Sum1 and Ndt80 proteins compete for binding to middle sporulation element sequences that control meiotic gene expression. Molecular and Cellular Biology 23: 4814–4825.

Rusche LN, Kirchmaier AL and Rine J (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annual Review of Biochemistry. 72: 481–516.

Rusche LN and Rine J (2001) Conversion of a gene‐specific repressor to a regional silencer. Genes & Development 15: 955–967.

Tham WH and Zakian VA (2002) Transcriptional silencing at Saccharomyces telomeres: implications for other organisms. Oncogene 21: 512–521.

Further Reading

Johnson AD (1995) The price of repression. Cell 81: 655–658.

Levine SS, King IF and Kingston RE (2004) Division of labor in polycomb group repression. Trends in Biochemical Sciences 29: 478–485.

Ptashne M (2004) A Genetic Switch, 3rd edn. Cambridge, MA: Cold Spring Harbor Laboratory Press.

Thiel G, Lietz M and Hohl M (2004) How mammalian transcriptional repressors work. European Journal of Biochemistry 271: 2855–2862.

Web Links The Cold Spring Harbor Laboratory – Dolan DNA Learning Center is devoted to genetics education beginning at the elementary school level and continuing through teacher education. The on‐line chapters address a range of diverse issues centered around molecular genetics, including genetic origins, genes and health, the molecular basis of cancer and mechanisms of gene silencing. The Saccharomyces Genome Database (SGD) provides a compendium of the genetics and molecular biology of baker's yeast, the experimental workhorse used to discover many fundamental aspects of eukaryotic biology. On‐line tools include access to the yeast genome sequence, software to analyse genes and their products, comparative sequence analyses, and even a comprehensive list of yeast molecular biologists. Comparable to SGD, the Mouse Genome Database (MGD) provides a comprehensive database of mouse genes, gene products and phenotypes. MGD interfaces with other bioinformatic databases, allowing for comparative genome analyses. The National Center for Biotechnology Information creates public databases, conducts research in computational biology, develops software tools for analysing genome data and disseminates biomedical information – all for the better understanding of molecular processes affecting human health and disease. The literature databases are an especially valuable function, allowing rapid and comprehensive searches through the National Library of Medicine.

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Hampsey, Michael(Dec 2007) Negative Regulatory Elements (NREs). In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005030.pub2]