Cis-regulatory element

A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA (often a chromosome). This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or more trans-acting factors. A cis-element may be located 5' to the coding sequence of the gene it controls (in the promoter region or further upstream), in an intron, or 3' to the gene's coding sequence, either in the untranslated or untranscribed region.

An example of a cis-acting regulatory sequence is the operator in the lac operon. This DNA sequence is bound by the lac repressor, which, in turn, prevents transcription of the adjacent genes on the same DNA molecule. The lac operator is, thus, considered to "act in cis" on the regulation of the nearby genes. The operator itself does not code for any protein or RNA.

In contrast, trans-regulatory elements are diffusible factors, usually proteins, that may modify the expression of genes distant from the gene that was originally transcribed to create them. For example, a transcription factor which regulates a gene on chromosome 6 might itself have been transcribed from a gene on chromosome 11. This term is constructed from the Latin root trans, which means "across from".

To summarize, cis-regulatory elements are present on the same molecule of DNA as the gene they regulate whereas trans-regulatory elements can regulate genes distant from the gene from which they were transcribed.

Examples of cis-regulatory elements in RNA

RNA elements

Type	Abbr.	Function	Distribution	Ref.
Frameshift element		Regulates alternative frame use with messenger RNAs	Archaea, Bacteria, Eukaryota, RNA viruses	[1][2][3]
Iron response element	IRE	Regulates the expression of iron associated genes	Eukaryota	[4]
Leader peptide		Regulates transcription of associated genes and/or operons	Bacteria	[5]
Internal ribosome entry site	IRES	Initiates translation in the middle of a messenger RNA	RNA virus, Eukaryota	[6]
Pyrrolysine insertion sequence	PYLIS	directs the cell to translate immediately adjacent UAG stop codons into pyrrolysine	Archaea	[7]
Riboswitch		Gene regulation	Bacteria, Eukaryota	[8]
Selenocysteine insertion sequence	SECIS	directs the cell to translate UGA stop-codons as selenocysteines	Metazoa	[9]

See also

• DNA
  • TATA box
  • Pribnow box
  • SOS box
  • CAAT box
  • CCAAT box
  • Operator (biology)
  • Upstream Activation Sequence
• RNA
  • List of cis-regulatory RNA elements
  • Polyadenylation signals, mRNA
  • AU-rich element, mRNA
• Other
  • Regulation of gene expression
  • cis-regulatory module
  • Gene regulatory network
  • Operon
  • Promoter
  • Trans-acting factor
  • Rfam
  • Transterm

References

1. ^ Bekaert M, Firth AE, Zhang Y, Gladyshev VN, Atkins JF, Baranov PV (2010). "Recode-2: new design, new search tools, and many more genes.". Nucleic Acids Res 38 (Database issue): D69–74. doi:10.1093/nar/gkp788. PMC 2808893. PMID 19783826. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2808893. 
2. ^ Chung BY, Firth AE, Atkins JF (2010). "Frameshifting in alphaviruses: a diversity of 3' stimulatory structures.". J Mol Biol 397 (2): 448–56. doi:10.1016/j.jmb.2010.01.044. PMID 20114053. 
3. ^ Giedroc DP, Cornish PV (2009). "Frameshifting RNA pseudoknots: structure and mechanism.". Virus Res 139 (2): 193–208. doi:10.1016/j.virusres.2008.06.008. PMC 2670756. PMID 18621088. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2670756. 
4. ^ Hentze MW, Kühn LC (August 1996). "Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8175–82. doi:10.1073/pnas.93.16.8175. PMC 38642. PMID 8710843. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38642. 
5. ^ Platt T (1986). "Transcription termination and the regulation of gene expression.". Annu Rev Biochem 55: 339–72. doi:10.1146/annurev.bi.55.070186.002011. PMID 3527045. 
6. ^ Mokrejs M, Vopálenský V, Kolenaty O, et al (January 2006). "IRESite: the database of experimentally verified IRES structures (www.iresite.org)". Nucleic Acids Res. 34 (Database issue): D125–30. doi:10.1093/nar/gkj081. PMC 1347444. PMID 16381829. http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16381829. 
7. ^ Théobald-Dietrich A, Giegé R, Rudinger-Thirion J (2005). "Evidence for the existence in mRNAs of a hairpin element responsible for ribosome dependent pyrrolysine insertion into proteins". Biochimie 87 (9-10): 813–7. doi:10.1016/j.biochi.2005.03.006. PMID 16164991. 
8. ^ Breaker RR (2008). "Complex riboswitches.". Science 319 (5871): 1795–7. doi:10.1126/science.1152621. PMID 18369140. 
9. ^ Walczak, R; Westhof E, Carbon P, Krol A (1996). "A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs". RNA 2 (4): 367–379. PMC 1369379. PMID 8634917. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1369379. 

Further reading

• Wray G. A. (2007). "The evolutionary significance of cis-regulatory mutations". Nature Reviews Genetics 8 (3): 206–216. doi:10.1038/nrg2063. PMID 17304246. 
• Gompel et al. (2005). "Chance caught on the wing: cis regulation evolution and the origin of pigmentation patterns in Drosophila". Nature 433 (7025): 481–487. doi:10.1038/nature03235. PMID 15690032. 
• Prud'homme et al. (2006). "Repeated morphological evolution through cis regulatory changes in a pleiotropic gene". Nature 440 (7087): 1050–1053. doi:10.1038/nature04597. PMID 16625197. 
• Stern D.L. (2000). "Perspective: Evolutionary developmental biology and the problem of variation". Evolution 54 (4): 1079–1091. PMID 11005278. 
• Weatherbee, Scott D.; Carroll, Sean B.; Grenier, Jennifer K. (2004). From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design. Cambridge, MA: Blackwell Publishers. ISBN 1-4051-1950-0.