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MeSH Review

Locus Control Region

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Disease relevance of Locus Control Region


High impact information on Locus Control Region

  • We show, in mice and humans, that a core ACH is developmentally conserved and consists of the hypersensitive sites (HS1-HS6) of the locus control region (LCR), the upstream 5' HS-60/-62 and downstream 3' HS1 [6].
  • The five human beta-type-globin genes, epsilon, Ggamma, Agamma, delta and beta, are close together and are regulated by a locus control region (LCR) located at the 5' end of the locus [7].
  • Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions [8].
  • Thus, the upstream DNA (previously named a dominant control or locus activation region, now denoted a locus control region) conferred the ability to express human beta-globin at high levels dependent on copy number on every mouse carrying the construct [9].
  • As described in this issue of Immunity, Lee et al. have now used a transgenic mouse assay to identify a locus control region (LCR) that supports integration site-independent, copy number-dependent transcription of Il4 and Il13 [10].

Biological context of Locus Control Region

  • We recently identified a 3' region of the rad50 gene possessing strong enhancer activity as well as activity consistent with function as a locus control region (LCR) for the flanking Th2 cytokine genes [11].
  • In addition to local sequence elements the regulation of the high-level, development- and tissue-specific expression of the human beta globin gene cluster appears to require distant regulatory sequences which have been termed locus control region [12].
  • Surprisingly, the beta-globin locus control region (LCR), although critical for high-level gene expression, plays little role in the overall architecture of the active locus [13].
  • The beta-globin locus control region (LCR) confers high levels of position-independent, copy number-dependent expression onto globin transgenes [14].
  • The 5'HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites [15].

Anatomical context of Locus Control Region


Associations of Locus Control Region with chemical compounds


Gene context of Locus Control Region


Analytical, diagnostic and therapeutic context of Locus Control Region


  1. Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells. Madisen, L., Groudine, M. Genes Dev. (1994) [Pubmed]
  2. Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network. Sun, J., Brand, M., Zenke, Y., Tashiro, S., Groudine, M., Igarashi, K. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. A chromatin insulator protects retrovirus vectors from chromosomal position effects. Emery, D.W., Yannaki, E., Tubb, J., Stamatoyannopoulos, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Imren, S., Payen, E., Westerman, K.A., Pawliuk, R., Fabry, M.E., Eaves, C.J., Cavilla, B., Wadsworth, L.D., Beuzard, Y., Bouhassira, E.E., Russell, R., London, I.M., Nagel, R.L., Leboulch, P., Humphries, R.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Rhabdomyosarcoma arising in transgenic mice harboring the beta-globin locus control region fused with simian virus 40 large T antigen gene. Teitz, T., Chang, J.C., Kitamura, M., Yen, T.S., Kan, Y.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. The beta-globin nuclear compartment in development and erythroid differentiation. Palstra, R.J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., de Laat, W. Nat. Genet. (2003) [Pubmed]
  7. Effects of altered gene order or orientation of the locus control region on human beta-globin gene expression in mice. Tanimoto, K., Liu, Q., Bungert, J., Engel, J.D. Nature (1999) [Pubmed]
  8. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Andrews, N.C., Erdjument-Bromage, H., Davidson, M.B., Tempst, P., Orkin, S.H. Nature (1993) [Pubmed]
  9. Site-independent expression of the chicken beta A-globin gene in transgenic mice. Reitman, M., Lee, E., Westphal, H., Felsenfeld, G. Nature (1990) [Pubmed]
  10. A Th2 cytokine LCR. Adding a new piece to the regulatory puzzle. Smale, S.T. Immunity (2003) [Pubmed]
  11. Th2-specific chromatin remodeling and enhancer activity in the Th2 cytokine locus control region. Fields, P.E., Lee, G.R., Kim, S.T., Bartsevich, V.V., Flavell, R.A. Immunity (2004) [Pubmed]
  12. The proximal element of the beta globin locus control region is not functionally required in vivo. Kulozik, A.E., Bail, S., Bellan-Koch, A., Bartram, C.R., Kohne, E., Kleihauer, E. J. Clin. Invest. (1991) [Pubmed]
  13. ChIPs of the beta-globin locus: unraveling gene regulation within an active domain. Bulger, M., Sawado, T., Schübeler, D., Groudine, M. Curr. Opin. Genet. Dev. (2002) [Pubmed]
  14. The beta-globin locus control region enhances transcription of but does not confer position-independent expression onto the lacZ gene in transgenic mice. Guy, L.G., Kothary, R., DeRepentigny, Y., Delvoye, N., Ellis, J., Wall, L. EMBO J. (1996) [Pubmed]
  15. The 5'HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites. Talbot, D., Grosveld, F. EMBO J. (1991) [Pubmed]
  16. Towards a transgenic mouse model of sickle cell disease: hemoglobin SAD. Trudel, M., Saadane, N., Garel, M.C., Bardakdjian-Michau, J., Blouquit, Y., Guerquin-Kern, J.L., Rouyer-Fessard, P., Vidaud, D., Pachnis, A., Roméo, P.H. EMBO J. (1991) [Pubmed]
  17. Retroviral transfer of a human beta-globin/delta-globin hybrid gene linked to beta locus control region hypersensitive site 2 aimed at the gene therapy of sickle cell disease. Takekoshi, K.J., Oh, Y.H., Westerman, K.W., London, I.M., Leboulch, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  18. Correct function of the locus control region may require passage through a nonerythroid cellular environment. Vassilopoulos, G., Navas, P.A., Skarpidi, E., Peterson, K.R., Lowrey, C.H., Papayannopoulou, T., Stamatoyannopoulos, G. Blood (1999) [Pubmed]
  19. The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus. Sengupta, P.K., Lavelle, D.E., DeSimone, J. Blood (1994) [Pubmed]
  20. In vivo footprinting of the human alpha-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction. Strauss, E.C., Andrews, N.C., Higgs, D.R., Orkin, S.H. Mol. Cell. Biol. (1992) [Pubmed]
  21. Dynamic regulation of histone H3 methylated at lysine 79 within a tissue-specific chromatin domain. Im, H., Park, C., Feng, Q., Johnson, K.D., Kiekhaefer, C.M., Choi, K., Zhang, Y., Bresnick, E.H. J. Biol. Chem. (2003) [Pubmed]
  22. Inhibition of Rho at different stages of thymocyte development gives different perspectives on Rho function. Cleverley, S., Henning, S., Cantrell, D. Curr. Biol. (1999) [Pubmed]
  23. Physical linkage of the human growth hormone gene family and the thyroid hormone receptor interacting protein-1 gene on chromosome 17. Surabhi, R.M., Bose, S., Kuschak, B.C., Cattini, P.A. Gene (1998) [Pubmed]
  24. A transgenic mouse model with inducible Tyrosinase gene expression using the tetracycline (Tet-on) system allows regulated rescue of abnormal chiasmatic projections found in albinism. Giménez, E., Lavado, A., Giraldo, P., Cozar, P., Jeffery, G., Montoliu, L. Pigment Cell Res. (2004) [Pubmed]
  25. Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Fiering, S., Epner, E., Robinson, K., Zhuang, Y., Telling, A., Hu, M., Martin, D.I., Enver, T., Ley, T.J., Groudine, M. Genes Dev. (1995) [Pubmed]
  26. Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions. Lee, G.R., Spilianakis, C.G., Flavell, R.A. Nat. Immunol. (2005) [Pubmed]
  27. Specification of unique Pit-1 activity in the hGH locus control region. Shewchuk, B.M., Liebhaber, S.A., Cooke, N.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  28. The binding of the ubiquitous transcription factor Sp1 at the locus control region represses the expression of beta-like globin genes. Feng, D., Kan, Y.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. Palmiter, R.D., Sandgren, E.P., Koeller, D.M., Brinster, R.L. Mol. Cell. Biol. (1993) [Pubmed]
  30. An "in-out" strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: analysis of the beta-globin locus control region. Fiering, S., Kim, C.G., Epner, E.M., Groudine, M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  31. SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression. Wen, J., Huang, S., Rogers, H., Dickinson, L.A., Kohwi-Shigematsu, T., Noguchi, C.T. Blood (2005) [Pubmed]
  32. Thalassaemia-like carriers not linked to the beta-globin gene cluster. Faà, V., Meloni, A., Moi, L., Ibba, G., Travi, M., Vitucci, A., Cao, A., Rosatelli, M.C. Br. J. Haematol. (2006) [Pubmed]
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