Locus Control Regions (LCRs)

Locus control regions (LCRs) are defined as DNA sequence elements that confer high-level, tissue-specific expression to stably integrated transgenes in a position-independent manner. As such, LCRs mediate gene activation and render a high proportion of genomic integration sites permissive for such expression, and are distinguished from simple enhancers.

Keywords: transcription; chromatin; enhancer; promoter; gene regulation

Figure 1. Expression in mice of transgenes containing different regulatory elements. A hypothetical transgene is integrated at random genomic sites in mice linked to only its promoter (left panel), the promoter and a classical enhancer (middle panel), or the promoter and a locus control region (LCR; right panel). The sorts of expression patterns that might be expected among different mice, each containing the transgene in a different integration site, in each case are shown: the darker the shading the higher the level of expression; no shading indicates no expression.
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 References
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    Bender MA, Bulger M, Close J and Groudine M (2000) Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region. Molecular Cell 5: 387–393.
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 Further Reading
    Blackwood EM and Kadonaga JT (1998) Going the distance: a current view of enhancer action. Science 281: 61–63.
    Bulger M and Groudine M (1999) Looping versus linking: toward a model for long-distance gene activation. Genes and Development 13: 2465–2477.
    Dorsett D (1999) Distant liaisons: long-range enhancer–promoter interactions in Drosophila. Current Opinion in Genetics and Development 9: 505–514.
    Ellis J, Tan-Un KC, Harper A, et al. (1996) A dominant chromatin-opening activity in 5¢ hypersensitive site 3 of the human beta-globin locus control region. EMBO Journal 15: 562–568.
    Festenstein R, Sharghi-Namini S, Fox M, et al. (1999) Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner. Nature Genetics 23: 457–461.
    Festenstein R, Tolaini M, Corbella P, et al. (1996) Locus control region function and heterochromatin-induced position effect variegation. Science 271: 1123–1125.
    Jenuwein T, Forrester WC, Fernandez-Herrero LA, et al. (1997) Extension of chromatin accessibility by nuclear matrix attachment regions. Nature 385: 269–272.
    Li Q, Harju S and Peterson KR (1999) Locus control regions: coming of age at a decade plus. Trends in Genetics 15: 403–408.
    McMorrow T, van den Wijngaard A, Wollenschlaeger A, et al. (2000) Activation of the beta globin locus by transcription factors and chromatin modifiers. EMBO Journal 19: 4986–4996.
    Travers A (1999) Chromatin modification by DNA tracking. Proceedings of the National Academy of Sciences of the United States of America 96: 13634–13637.
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How to Cite close
Bulger, Michael, and Groudine, Mark(Sep 2005) Locus Control Regions (LCRs). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005034]