Locus Control Regions (LCRs)


Locus control regions (LCRs) are defined as deoxyribonucleic acid 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 transcriptional enhancers, which like LCRs are capable of mediating gene activation over large genomic distances. The mechanistic basis for the functional distinction between LCRs and enhancers is unclear. LCRs appear to subsume the separate functions of both transcriptional enhancers and chromatin insulators, but may be qualitatively different from either of these classes of regulatory elements. At their native loci, however, LCRs may only be required for a subset of the activities that they display in transgenic contexts.

Key Concepts:

  • LCRs are cis‐acting DNA regulatory elements that have been identified at a number of tissue‐specific gene loci in vertebrates.

  • LCRs are defined by their activity in transgenic assays, where in addition to activating transcription of linked transgenes, they are capable of rendering most integration sites permissive for expression.

  • The mechanistic basis for LCR function in transgenes is unknown, and there is evidence both for LCRs representing simply a very strong enhancer and for LCRs harbouring an activity entirely distinct from that of enhancers, involving the long‐range propagation of an ‘open’ chromatin structure.

  • At the endogenous loci from which LCRs have been derived, they appear to be required for a variety of different functions, not all of which correspond to their activity in transgenes.

  • LCR function has been correlated with the regulation of nuclear localisation of linked genes.

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 (a), the promoter and a classical enhancer (b), or the promoter and a (LCR; (c)). 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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Further Reading

Barkness G and West A (2012) Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics 4: 67–80.

Buecker C and Wysocka J (2012) Enhancers as information integration hubs in development: lessons from genomics. Trends in Genetics 28: 276–284.

Dean A (2006) On a chromosome far, far away: LCRs and gene expression. Trends in Genetics 22: 38–45.

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.

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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.

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How to Cite close
Bulger, Michael, and Groudine, Mark(Jun 2013) Locus Control Regions (LCRs). In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005034.pub2]