Locus central regions and epigenetic chromatin modifiers

Current Opinion in Genetics and Development

Volumn 10, Issue 2, 2000, Pages 199-203

  Festenstein, Richard ^a   Kioussis, Dimitris ^b  

^a IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^b NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHROMATIN; CIS TRANS ISOMERISM; GENE ACTIVATION; GENE SILENCING; HETEROCHROMATIN; HUMAN; NONHUMAN; PRIORITY JOURNAL; REGULATOR GENE; REVIEW; TRANSGENIC MOUSE; ANIMAL; GENE EXPRESSION REGULATION; GENETICS;

MUS MUSCULUS;

ANIMALS; CHROMATIN; GENE EXPRESSION REGULATION; HUMANS; LOCUS CONTROL REGION;

EID: 0033624825     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(00)00060-5     Document Type: Review

References (58)

1. Grosveld F., van Assendelft G.B., Greaves D.R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 51:1987;975-985.
2. Kioussis D., Festenstein R. Locus control regions: overcoming heterochromatin-induced gene inactivation in mammals. Curr Opin Genet Dev. 7:1997;614-619.
3. Sabbattini P., Georgiou A., Sinclair C., Dillon N. Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda5-VpreB1 locus control region. Mol Cell Biol. 19:1999;671-679.
4. Raguz S., Hobbs C., Yague E., Ioannou P.A., Walsh F.S., Antoniou M. Muscle-specific locus control region activity associated with the human desmin gene. Dev Biol. 201:1998;26-42.
5. Bulger M., Groudine M. Looping versus linking: toward a model for long-distance gene activation. Genes Dev. 13:1999;2465-2477.
6. Grosveld F. Activation by locus control regions? Curr Opin Genet Dev. 9:1999;152-157. The authors discuss different models of LCR function and present results of data that demonstrate that changing the concentration of the transcription factor EKLF affects the extent of variegation of a human β-globin transgene. This is the first example of an activator shown to modify mammalian PEV in vivo.
7. Li Q., Harju S., Peterson K.R. Locus control regions: coming of age at a decade plus. Trends Genet. 15:1999;403-408.
8. Higgs D.R. Do LCRs open chromatin domains? Cell. 95:1998;299-302.
9. Heitz E. Das Heterochromatin der Moose. I Jahrb Wiss Botanik. 69:1928;762-818. [Title translation: Heterochromatin of moss.].
10. Muller H.J. Types of visible variations induced by X-rays in Drosophila. J Genet. 22:1930;299-334.
11. Henikoff S. Position effect variegation after 60 years. Trends Genet. 6:1990;422-426.
12. Grigliatti T. Position-effect variegation - an assay for nonhistone chromosomal proteins and chromatin assembly and modifying factors. Methods Cell Biol. 35:1991;587-627.
13. Reuter G., Spierer P. Position effect variegation and chromatin proteins. Bioessays. 14:1992;605-612.
14. Alberts B., Sternglanz R. Chromatin contract to silence. Nature. 344:1990;193-194.
15. Allshire R.C., Javerzat J-P., Redhead N.J., Cranston G. Position effect variegation at fission yeast centromeres. Cell. 76:1994;157-169.
16. Cattanach B.M. Position effect variegation in the mouse. Genet Res Camb. 23:1974;291-306.
17. Pravtcheva D.D., Wise T.L., Ensor N.J., Ruddle F.H. Mosaic expression of an Hprt transgene integrated in a region of Y heterochromatin. J Exp Zool. 268:1994;452-468.
18. Festenstein R., Tolaini M., Corbella P., Mamalaki C., Parrington J., Fox M., Miliou A., Jones M., Kioussis D. Locus control region function and heterochromatin-induced position effect variegation. Science. 271:1996;1123-1125.
19. Milot E., Strouboulis J., Trimborn T., Wijgerde M., de Boer E., Langeveld A., Tan-Un K., Vergeer W., Yannoutsos N., Grosveld F., Fraser P. Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell. 87:1996;105-114.
20. Singh P.B. Molecular mechanisms of cellular determination: their relation to chromatin structure. J Cell Sci. 107:1994;2653-2668.
21. Wakimoto B.T. Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila. Cell. 93:1998;321-324.
22. Kioussis D., Festenstein R. Position effect variegation and locus control regions and the regulation of lineage specific gene expression. Monroe J.G., Rothenburg E., Totowa N.J. Molecular Biology of B-Cell and T-Cell Development. 1998;Humana Press.
23. Karpen G.H. Position effect variegation and the new biology of heterochromatin. Curr Opin Genet Dev. 4:1994;281-291.
24. Eissenberg J.C., James T.C., Foster-Hartnett D.M., Hartnett T., Ngan V., Elgin S.C. Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc Natl Acad Sci USA. 87:1990;9923-9927.
25. Elgin S.C. Heterochromatin and gene regulation in Drosophila. Curr Opin Genet Dev. 6:1996;193-202.
26. De Rubertis F., Kadosh D., Henchoz S., Pauli D., Reuter G., Struhl K., Spierer P. The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast. Nature. 384:1996;589-591.
27. Kim J., Sif S., Jones B., Jackson A., Koipally J., Heller E., Winandy S., Viel A., Sawyer A., Ikeda T.et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity. 10:1999;345-355. This paper describes the biochemical purification of a multimeric protein complex containing the Ikaros protein and demonstrates that this complex has chromatin remodelling activity. The authors conclude that the lymphoid transcription factor Ikaros recruits a histone deacetylase and a DNA-dependent kinase (Mi-2) to heterochromatin upon T-cell activation.
28. Aagaard L., Laible G., Selenko P., Schmid M., Dorn R., Schotta G., Kuhfittig S., Wolf A., Lebersorger A., Singh P.B.et al. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. EMBO J. 18:1999;1923-1938.
29. Brown K.E., Guest S.S., Smale S.T., Hahm K., Merkenschlager M., Fisher A.G. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell. 91:1997;845-854.
30. Brown K.E., Baxter J., Graf D., Merkenschlager M., Fisher A.G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol Cell. 3:1999;207-217. Using 'immunofish' to visualise specific heterochromatin-associated proteins and genes simultaneously in interphase nuclei, the authors demonstrate that following T-cell activation the Tdt and rag genes are silenced and then relocalised to centromeric heterochromatin. They suggest that heterochromatic localisation prior to cell division may be required for the heritability of the silenced state.
31. Cockell M., Gasser S.M. Nuclear compartments and gene regulation. Curr Opin Genet Dev. 9:1999;199-205.
32. Cskink A.M., Henikoff S. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature. 381:1996;529-531.
33. Dernburg A.F., Broman K.W., Fung J.C., Marshall W.F., Philips J., Agard D.A., Sedat J.W. Pertubation of nuclear architecture by long-distance chromosome interactions. Cell. 85:1996;745-759.
34. Riggs A.D., Pfeifer G.P. X-chromosome inactivation and cell memory. Trends Genet. 8:1992;169-174.
35. Francastel C., Walters M.C., Groudine M., Martin D.I.K. A functional enhancer suppresses silencing of a transgene and prevents its localisation close to centromeric heterochromatin. Cell. 99:1999;259-269. This paper describes a series of experiments using gene constructs driven by mutated versions of a subunit of the β-globin (HSS 2) LCR integrated into particular locations in the genome. The authors demonstrate that individual transcription factor binding sites are required for gene activation at a specific chromosomal location. They also demonstrate, using fluorescence in situ hybridisation of interphase nuclei, that the presence of this LCR subregion excludes the locus from centromeric heterochromatin.
36. Walters M.C., Magis W., Fiering S., Eidemiller J., Scalzo D., Groudine M., Martin D.I. Transcriptional enhancers act in cis to suppress position-effect variegation. Genes Dev. 10:1996;185-195.
37. Walters M.C., Fiering S., Eidemiller J., Magis W., Groudine M., Martin D.I.K. Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci USA. 92:1995;7125-7129.
38. Guy L.G., Kothary R., DeRepentigny Y., Delvoye N., Ellis J., Wall L. The beta-globin locus control region enhances transcription of but does not confer position-independent expression onto the lacZ gene in transgenic mice. EMBO J. 15:1996;3713-3721.
39. Guy L.G., Kothary R., Wall L. Position effects in mice carrying a lacZ transgene in cis with the beta-globin LCR can be explained by a graded model. Nucleic Acids Res. 25:1997;4400-4407.
40. Reik A., Telling A., Zitnik G., Cimbora D., Epner E., Groudine M. The locus control region is necessary for gene expression in the human beta-globin locus but not the maintenance of an open chromatin structure in erythroid cells. Mol Cell Biol. 18:1998;5992-6000.
41. Garrick D., Fiering S., Martin D.I., Whitelaw E. Repeat-induced gene silencing in mammals. Nat Genet. 18:1998;56-59.
42. Aparicio O.M., Gottschling D.E. Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way. Genes Dev. 8:1994;1133-1146.
43. Festenstein R., Sharghi-Namini S., Fox M., Roderick K., Norton T., Saveliev A., Kioussis D., Singh P. Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner. Nat Genet. 23:1999;457-461. In this paper, human CD2 transgenic mice with their transgenes linked to full LCRs (non-variegating) or disabled LCRs (variegating) are crossed to transgenic mice that overexpress Heterochromatin protein 1 (M31). The authors show that overexpression of this component of heterochromatin increases the proportion of T cells that take the decision to silence the hCD2 transgene when the transgene is located at the centromere. In addition, they describe one transgenic line that variegates despite being located in the chromosomal long arm; M31 overexpression in this case decreases the proportion of cells that take the decision to silence the hCD2 transgene.
44. Zhuma T., Tyrrell R., Sekkali B., Skavdis G., Saveliev A., Tolaini M., Roderick K., Norton T., Smerdon S., Sedgwick S.et al. Human HMG box transcription factor HBP1: a role in hCD2 LCR function. EMBO J. 18:1999;6396-6406. The authors identify a DNA binding site for the transcription factor HBP1 within a subregion of the hCD2 LCR required for enabling position independent expression. They analyse the effect on gene expression after deleting this binding site in transgenic mice. The conclusion is that this binding site is not necessary for hypersensitive site formation but that its deletion renders the transgene susceptible to centromeric PEV.
45. Wreggett K.A., Hill F., James P.S., Hutchings A., Butcher G.W., Singh P.B. A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin. Cytogenet Cell Genet. 66:1994;99-103.
46. Lu B.Y., Bishop C.P., Eissenberg J.C. Developmental timing and tissue specificity of heterochromatin-mediated silencing. EMBO J. 15:1996;1323-1332.
47. Wakimoto B.T., Hearn M.G. The effects of chromosome rearrangement on the expression of heterochromosomal genes in chromosome 2L in D. melanogaster. Genetics. 125:1990;141-154.
48. Khavari P.A., Peterson C.L., Tamkun J.W., Mendel D.B., Crabtree G.R. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature. 366:1993;170-174.
49. Singh P.B., Huskisson N.S. Chromatin complexes as aperiodic microcrystalline arrays that regulate genome organisation and expression. Dev Genet. 22:1998;85-99.
50. Armstrong J.A., Bieker J.J., Emerson B.M. A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro. Cell. 95:1998;93-104.
51. Gillemans N., Tewari R., Lindeboom F., Rottier R., de Wit T., Wijgerde M., Grosveld F., Philipsen S. Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta-globin locus control region in vivo. Genes Dev. 12:1998;2863-2873.
52. Lake R.A., Wotton D.M.J. A 3′ transcriptional enhancer regulates tissue-specific expression of the human CD2 gene. EMBO J. 9:1990;3129-3136.
53. + transport defective yeast and distribution of HBP1, a new putative HMG transcriptional regulator. Nucleic Acids Res. 22:1994;3685-3688.
54. Pil P.M., Chow C.S., Lippard S.J. High-mobility-group 1 protein mediates DNA bending as determined by ring closures. Proc Natl Acad Sci USA. 90:1993;9465-9469.
55. Haynes T.L., Thomas M.B., Dusing M.R., Valerius M.T., Potter S.S., Wiginton D.A. An enhancer LEF-1/TCF-1 site is essential for insertion site-independent transgene expression in thymus. Nucleic Acids Res. 24:1996;5034-5044.
56. Gottschling D.E., Aparicio O.M., Billington B.L., Zakian V.A. Position effect at S. cerevisiae telomeres: reversible repression of pol II transcription. Cell. 63:1990;751-762.
57. Epner E., Reik A., Cimbora D., Telling A., Bender M.A., Fiering S., Enver T., Martin D.I., Kennedy M., Keller G., Groudine M. The beta-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse beta-globin locus. Mol Cell. 2:1998;447-455. The effects of the deletion of the mouse β-globin LCR in ES cells is studied after in vitro differentiation and after transfer to a human erythroid cell line. The authors analyse expression and DNAse I sensitivity and conclude that the LCR has a contributory rather than dominant function.
58. Ronai D., Berru M., Shulman M.J. Variegated expression of the endogenous immunoglobulin heavy-chain gene in the absence of the intronic locus control region. Mol Cell Biol. 19:1999;7031-7040.