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Locus Control Regions (LCRs)

  1. Michael Bulger,
  2. Mark Groudine

Published Online: 13 JUN 2013

DOI: 10.1002/9780470015902.a0005034.pub2

eLS

eLS

How to Cite

Bulger, M. and Groudine, M. 2013. Locus Control Regions (LCRs). eLS. .

Author Information

  1. University of Rochester, Rochester, New York, USA

Publication History

  1. Published Online: 13 JUN 2013

Abstract

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