Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Decision making in the immune system

Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation

Nature Reviews Immunology volume 2, pages 909–919 (2002)Cite this article

An Erratum to this article was published on 01 January 2003

Key Points

  • During T-cell development, immature double-positive (DP) CD4+CD8+ thymocytes develop mainly into two subsets of T cell — MHC class-II-restricted CD4+ helper T cells and MHC class-I-restricted CD8+ cytotoxic T cells.

  • Factors that are involved in the transcriptional regulation of CD4, and CD8A and CD8B genes might be involved in directing the cell fate of a DP thymocyte towards either lineage.

  • Cis elements (such as promoters and enhancers) and trans elements (such as transcription factors and chromatin-remodelling complexes) contribute to the generation of chromatin structures that control the complex pattern of CD4, CD8A and CD8B gene expression.

  • The CD4 locus includes promoter, enhancer and silencer elements that regulate CD4 gene expression. The CD8A and CD8B gene complex is outlined, and CD8 regulatory elements and enhancer-binding factors are discussed. Does a CD8 silencer exist?

  • Modifications of cis- and trans-acting elements influence the chromatin structure of the CD4, CD8A and CD8B loci, including DNA methylation and histone acetylation. Other nuclear proteins, including high-mobility group (HMG)-box-containing proteins and Ikaros are involved also.

Abstract

The regulation of gene expression during thymocyte development provides an ideal experimental system to study lineage-commitment processes. In particular, expression of the CD4, CD8A and CD8B genes seems to correlate well with the cell-fate decisions that are taken by thymocytes, and elucidating the molecular mechanisms that underlie the differential expression of these genes could reveal key events in differentiation processes. Here, we review examples of how gene cis elements (such as promoters, enhancers and locus control regions) and trans elements (such as transcription factors, chromatin-remodelling complexes and histone-modification enzymes) come together to orchestrate a finely tuned sequence of events that results in the complex pattern of CD4, CD8A and CD8B gene expression that is observed during thymocyte development.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A simple model of T-cell development.
Figure 2: Chromatin remodelling.
Figure 3: The mouse Cd4 locus: transgenic constructs and silencer deletions.
Figure 4: The mouse Cd8a and Cd8b gene complex: transgenic constructs and enhancer deletions.
Figure 5: Possible chromatin states of CD4, CD8A and CD8B during thymocyte differentiation.

Similar content being viewed by others

References

  1. Germain, R. N. T-cell development and the CD4–CD8 lineage decision. Nature Rev. Immunol. 2, 309–322 (2002).

    Article  CAS  Google Scholar 

  2. Basson, M. A. & Zamoyska, R. The CD4/CD8 lineage decision: integration of signalling pathways. Immunol. Today 21, 509–514 (2000).

    Article  CAS  Google Scholar 

  3. Singer, A. New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision. Curr. Opin. Immunol. 14, 207–215 (2002).

    Article  CAS  Google Scholar 

  4. Hedrick, S. M. T-cell development: bottoms-up. Immunity 16, 619–622 (2002).

    Article  CAS  Google Scholar 

  5. Wolffe, A. P. Transcriptional regulation in the context of chromatin structure. Essays Biochem. 37, 45–57 (2001).

    Article  CAS  Google Scholar 

  6. Dillon, N. & Festenstein, R. Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet. 18, 252–258 (2002).

    Article  CAS  Google Scholar 

  7. Gross, D. S. & Garrard, W. T. Nuclease hypersensitive sites in chromatin. Annu. Rev. Biochem. 57, 159–197 (1988).

    Article  CAS  Google Scholar 

  8. Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002).

    Article  CAS  Google Scholar 

  9. Berger, S. L. Histone modifications in transcriptional regulation. Curr. Opin. Genet. Dev. 12, 142–148 (2002).

    Article  CAS  Google Scholar 

  10. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).

    Article  CAS  Google Scholar 

  11. Aalfs, J. D. & Kingston, R. E. What does 'chromatin remodeling' mean? Trends Biochem. Sci. 25, 548–555 (2000).

    Article  CAS  Google Scholar 

  12. Gillespie, F. P. et al. Tissue-specific expression of human CD4 in transgenic mice. Mol. Cell. Biol. 13, 2952–2958 (1993).

    Article  CAS  Google Scholar 

  13. Killeen, N., Sawada, S. & Littman, D. R. Regulated expression of human CD4 rescues helper T-cell development in mice lacking expression of endogenous CD4. EMBO J. 12, 1547–1553 (1993).

    Article  CAS  Google Scholar 

  14. Hanna, Z., Simard, C., Laperriere, A. & Jolicoeur, P. Specific expression of the human CD4 gene in mature CD4+CD8− and immature CD4+CD8+ T cells and in macrophages of transgenic mice. Mol. Cell. Biol. 14, 1084–1094 (1994).

    Article  CAS  Google Scholar 

  15. Sawada, S., Scarborough, J. D., Killeen, N. & Littman, D. R. A lineage-specific transcriptional silencer regulates CD4 gene expression during T-lymphocyte development. Cell 77, 917–929 (1994).

    Article  CAS  Google Scholar 

  16. Siu, G., Wurster, A. L., Duncan, D. D., Soliman, T. M. & Hedrick, S. M. A transcriptional silencer controls the developmental expression of the CD4 gene. EMBO J. 13, 3570–3579 (1994).

    Article  CAS  Google Scholar 

  17. Leung, R. K. et al. Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment. Nature Immunol. 2, 1167–1173 (2001).

    Article  CAS  Google Scholar 

  18. Zou, Y. R. et al. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nature Genet. 29, 332–336 (2001). References 17 and 18 describe the consequences of deletion of the silencer sequences from the germline or at discrete stages of development in the mouse on the expression of the Cd4 gene. In particular, reference 18 indicates that the silencer is required for the initiation, but not maintenance, of Cd4 silencing in cytotoxic T cells, which indicates that there is epigenetic regulation of Cd4 gene expression in mature T cells.

    Article  CAS  Google Scholar 

  19. Ellmeier, W., Sawada, S. & Littman, D. R. The regulation of CD4 and CD8 coreceptor gene expression during T-cell development. Annu. Rev. Immunol. 17, 523–554 (1999).

    Article  CAS  Google Scholar 

  20. Zhuang, Y., Cheng, P. & Weintraub, H. B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2 and HEB. Mol. Cell. Biol. 16, 2898–2905 (1996).

    Article  CAS  Google Scholar 

  21. Wurster, A. L., Siu, G., Leiden, J. M. & Hedrick, S. M. Elf-1 binds to a critical element in a second CD4 enhancer. Mol. Cell. Biol. 14, 6452–6463 (1994).

    Article  CAS  Google Scholar 

  22. Salmon, P., Boyer, O., Lores, P., Jami, J. & Klatzmann, D. Characterization of an intronless CD4 minigene expressed in mature CD4 and CD8 T cells, but not expressed in immature thymocytes. J. Immunol. 156, 1873–1879 (1996).

    CAS  PubMed  Google Scholar 

  23. Adlam, M., Duncan, D. D., Ng, D. K. & Siu, G. Positive selection induces CD4 promoter and enhancer function. Int. Immunol. 9, 877–887 (1997).

    Article  CAS  Google Scholar 

  24. Boyer, O. et al. Position-dependent variegation of a CD4 minigene with targeted expression to mature CD4+ T cells. J. Immunol. 159, 3383–3390 (1997).

    CAS  PubMed  Google Scholar 

  25. Uematsu, Y., Donda, A. & De Libero, G. Thymocytes control the CD4 gene differently from mature T lymphocytes. Int. Immunol. 9, 179–187 (1997).

    Article  CAS  Google Scholar 

  26. Sawada, S. & Littman, D. R. Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene. Mol. Cell. Biol. 11, 5506–5515 (1991).

    Article  CAS  Google Scholar 

  27. Blum, M. D., Wong, G. T., Higgins, K. M., Sunshine, M. J. & Lacy, E. Reconstitution of the subclass-specific expression of CD4 in thymocytes and peripheral T cells of transgenic mice: identification of a human CD4 enhancer. J. Exp. Med. 177, 1343–1358 (1993).

    Article  CAS  Google Scholar 

  28. Duncan, D. D., Adlam, M. & Siu, G. Asymmetric redundancy in CD4 silencer function. Immunity 4, 301–311 (1996).

    Article  CAS  Google Scholar 

  29. Kim, H. K. & Siu, G. The notch pathway intermediate HES-1 silences CD4 gene expression. Mol. Cell. Biol. 18, 7166–7175 (1998).

    Article  CAS  Google Scholar 

  30. Kim, W. W. & Siu, G. Subclass-specific nuclear localization of a novel CD4 silencer binding factor. J. Exp. Med. 190, 281–291 (1999).

    Article  CAS  Google Scholar 

  31. Allen, R. D. 3rd, Kim, H. K., Sarafova, S. D. & Siu, G. Negative regulation of CD4 gene expression by a HES-1–c-Myb complex. Mol. Cell. Biol. 21, 3071–3082 (2001).

    Article  CAS  Google Scholar 

  32. Taniuchi, I., Sunshine, M. J., Festenstein, R. & Littman, D. R. Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol Cell 10, 1083–1096 (2002).

    Article  CAS  Google Scholar 

  33. Jarry, A., Cerf-Bensussan, N., Brousse, N., Selz, F. & Guy-Grand, D. Subsets of CD3+ (T-cell receptor αβ or γδ) and CD3− lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur. J. Immunol. 20, 1097–1103 (1990).

    Article  CAS  Google Scholar 

  34. Lefrancois, L. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J. Immunol. 147, 1746–1751 (1991).

    CAS  PubMed  Google Scholar 

  35. Vremec, D. et al. The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. J. Exp. Med. 176, 47–58 (1992).

    Article  CAS  Google Scholar 

  36. Gorman, S. D., Sun, Y. H., Zamoyska, R. & Parnes, J. R. Molecular linkage of the Ly-3 and Ly-2 genes. Requirement of Ly-2 for Ly-3 surface expression. J. Immunol. 140, 3646–3653 (1988).

    CAS  PubMed  Google Scholar 

  37. Hostert, A. et al. A CD8 genomic fragment that directs subset-specific expression of CD8 in transgenic mice. J. Immunol. 158, 4270–4281 (1997).

    CAS  PubMed  Google Scholar 

  38. Kieffer, L. J., Yan, L., Hanke, J. H. & Kavathas, P. B. Appropriate developmental expression of human CD8β in transgenic mice. J. Immunol. 159, 4907–4912 (1997).

    CAS  PubMed  Google Scholar 

  39. Ellmeier, W., Sunshine, M. J., Losos, K., Hatam, F. & Littman, D. R. An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells. Immunity 7, 537–547 (1997).

    Article  CAS  Google Scholar 

  40. Ellmeier, W., Sunshine, M. J., Losos, K. & Littman, D. R. Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells. Immunity 9, 485–496 (1998).

    Article  CAS  Google Scholar 

  41. Hostert, A. et al. A region in the CD8 gene locus that directs expression to the mature CD8 T-cell subset in transgenic mice. Immunity 7, 525–536 (1997).

    Article  CAS  Google Scholar 

  42. Hostert, A. et al. Hierachical interactions of control elements determine CD8a gene expression in subsets of thymocytes and peripheral T cells. Immunity 9, 497–508 (1998).

    Article  CAS  Google Scholar 

  43. Kieffer, L. J. et al. Human CD8α expression in NK cells but not cytotoxic T cells of transgenic mice. Int. Immunol. 8, 1617–1626 (1996).

    Article  CAS  Google Scholar 

  44. Zhang, X. L. et al. Distinct stage-specific cis-active transcriptional mechanisms control expression of T-cell coreceptor CD8α at double- and single-positive stages of thymic development. J. Immunol. 161, 2254–2266 (1998).

    CAS  PubMed  Google Scholar 

  45. Zhang, X. L. et al. CD8 expression up to the double-positive CD3(low/intermediate) stage of thymic differentiation is sufficient for development of peripheral functional cytotoxic T lymphocytes. J. Exp. Med. 194, 685–693 (2001).

    Article  CAS  Google Scholar 

  46. Ellmeier, W., Sunshine, M. J., Maschek, R. & Littman, D. R. Combined deletion of CD8 locus cis-regulatory elements affects initiation, but not maintenance, of CD8 expression. Immunity 16, 623–634 (2002).

    Article  CAS  Google Scholar 

  47. Garefalaki, A. et al. Variegated expression of CD8α resulting from in situ deletion of regulatory sequences. Immunity 16, 635–647 (2002). References 46 and 47 show that the expression of CD8 in double-positive (DP) thymocytes is variegated in the absence of certain cis -regulatory elements, which indicates that these cis elements at the CD8A and CD8B loci are required for the proper initiation of CD8 expression in all thymocytes that make the transition from double-negative to DP stages of differentiation. Most probably, this is achieved by recruiting chromatin-opening activities.

    Article  CAS  Google Scholar 

  48. Robertson, K. D. DNA methylation and chromatin — unraveling the tangled web. Oncogene 21, 5361–5379 (2002).

    Article  CAS  Google Scholar 

  49. Fraser, P., Pruzina, S., Antoniou, M. & Grosveld, F. Each hypersensitive site of the human β-globin locus control region confers a different developmental pattern of expression on the globin genes. Genes Dev. 7, 106–113 (1993).

    Article  CAS  Google Scholar 

  50. Greaves, D. R., Wilson, F. D., Lang, G. & Kioussis, D. Human CD2 3′-flanking sequences confer high-level, T-cell-specific, position-independent gene expression in transgenic mice. Cell 56, 979–986 (1989).

    Article  CAS  Google Scholar 

  51. Davie, J. R. The nuclear matrix and the regulation of chromatin organization and function. Int. Rev. Cytol. 162A, 191–250 (1995).

    CAS  PubMed  Google Scholar 

  52. Scheuermann, R. H. & Garrard, W. T. MARs of antigen receptor and co-receptor genes. Crit. Rev. Eukaryot. Gene Expr. 9, 295–310 (1999).

    Article  CAS  Google Scholar 

  53. Tutt Landolfi, M. M., Scollay, R. & Parnes, J. R. Specific demethylation of the CD4 gene during CD4 T-lymphocyte differentiation. Mol. Immunol. 34, 53–61 (1997).

    Article  CAS  Google Scholar 

  54. Carbone, A. M., Marrack, P. & Kappler, J. W. Remethylation at sites 5′ of the murine Lyt-2 gene in association with shutdown of Lyt-2 expression. J. Immunol. 141, 1369–1375 (1988).

    CAS  PubMed  Google Scholar 

  55. Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T-cell development, function and survival. Immunity 15, 763–774 (2001).

    Article  CAS  Google Scholar 

  56. Brown, K. E. et al. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91, 845–854 (1997).

    Article  CAS  Google Scholar 

  57. Cobb, B. S. et al. Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding. Genes Dev. 14, 2146–2160 (2000).

    Article  CAS  Google Scholar 

  58. Kramer, J. A., Singh, G. B. & Krawetz, S. A. Computer-assisted search for sites of nuclear matrix attachment. Genomics 33, 305–308 (1996).

    Article  CAS  Google Scholar 

  59. Alvarez, J. D. et al. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 14, 521–535 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Banan, M. et al. Interaction of the nuclear matrix-associated region (MAR)-binding proteins, SATB1 and CDP/Cux, with a MAR element (L2a) in an upstream regulatory region of the mouse CD8a gene. J. Biol. Chem. 272, 18440–18452 (1997).

    Article  CAS  Google Scholar 

  61. Kieffer, L. J. et al. Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3. J. Immunol. 168, 3915–3922 (2002).

    Article  CAS  Google Scholar 

  62. Grosschedl, R., Giese, K. & Pagel, J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 10, 94–100 (1994).

    Article  CAS  Google Scholar 

  63. Zhuma, T. et al. Human HMG-box transcription factor HBP1: a role in hCD2 LCR function. EMBO J. 18, 6396–6406 (1999).

    Article  CAS  Google Scholar 

  64. Schilham, M. W. et al. Critical involvement of Tcf-1 in expansion of thymocytes. J. Immunol. 161, 3984–3991 (1998).

    CAS  PubMed  Google Scholar 

  65. Okamura, R. M. et al. Redundant regulation of T-cell differentiation and TCRα gene expression by the transcription factors LEF-1 and TCF-1. Immunity 8, 11–20 (1998).

    Article  CAS  Google Scholar 

  66. Wilkinson, B. et al. TOX: an HMG box protein implicated in the regulation of thymocyte selection. Nature Immunol. 3, 272–280 (2002).

    Article  CAS  Google Scholar 

  67. Chi, T. H. et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 418, 195–199 (2002). This study describes the changes in expression of CD4 and CD8 during thymocyte development that occur when components of the SWI/SNF-like chromatin-remodelling complex BAF are deleted from the mouse genome.

    Article  CAS  Google Scholar 

  68. Wilson, C. B., Makar, K. W. & Perez-Melgosa, M. Epigenetic regulation of T-cell fate and function. J. Infect. Dis. 185, S37–S45 (2002). This review offers an up-to-date, clear and concise description of chromatin changes in lymphocytes, including mature T cells.

    Article  CAS  Google Scholar 

  69. Georgopoulos, K. Haematopoietic cell-fate decisions, chromatin regulation and Ikaros. Nature Rev. Immunol. 2, 162–174 (2002).

    Article  CAS  Google Scholar 

  70. Kim, J. et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10, 345–355 (1999).

    Article  CAS  Google Scholar 

  71. Harker, N. et al. The CD8 gene locus is regulated by the Ikaros family of proteins. Mol. Cell. 2 December 2002 (DOI: 10.1016/S1097276502007116). This study describes the role of Ikaros-family proteins in activation of the CD8A gene during the transition from double-negative to double-positive thymocyte stages.

  72. Wang, J. H. et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 5, 537–549 (1996).

    Article  CAS  Google Scholar 

  73. Gorman, S. D., Tourvieille, B. & Parnes, J. R. Structure of the mouse gene encoding CD4 and an unusual transcript in brain. Proc. Natl. Acad. Sci. U.S.A. 84, 7644–7648 (1987).

    Article  CAS  Google Scholar 

  74. Sands, J. F. & Nikolic-Zugic, J. T-cell-specific protein–DNA interactions occurring at the CD4 locus: identification of possible transcriptional control elements of the murine CD4 gene. Int. Immunol. 4, 1183–1194 (1992).

    Article  CAS  Google Scholar 

  75. Taniuchi, I. et al. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T-lymphocyte development. Cell 111, 621–634 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to apologize to those colleagues whose original work could not be discussed owing to space limitations. We also thank our colleagues A. Cerwenka, A. O'Garra, G. Stockinger, V. Tybulewicz and R. Zamoyska for comments and suggestions on the manuscript. Work in the laboratory of D.K. is supported by the Medical Research Council, UK, the Leukaemia Research Fund, UK, and the European Union; work in the laboratory of W.E. is supported by the START programme and a research grant from the Austrian Research Fund, the Austrian Academies of Sciences, and by the BMT Vienna.

Author information

Authors and Affiliations

  1. Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, NW7 1AA, UK

    Dimitris Kioussis

  2. Institute of Immunology, University of Vienna, Brunner Straβe 59, Vienna, 1235, Austria

    Wilfried Ellmeier

Authors
  1. Dimitris Kioussis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wilfried Ellmeier
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

LocusLink

BAF57

BRG1

CD4

CD8A

CD8B

CD25

CD44

DNase I

DNMT1

E2A

H1

H2A

H2B

H3

H4

HAT

hBRM

HDAC1

HEB

Ikaros

LAG3

LEF1

RUNX1

RUNX3

SAF

SATB1

TCF1

TOX

Glossary

PROMOTER

The regulatory region of DNA to which RNA polymerase binds to initiate transcription.

ENHANCER

A control element to which regulatory proteins bind, thereby influencing the rate of gene transcription. Enhancers function in an orientation- and position-independent manner (they can act either upstream or downstream of a gene, or in an intron).

EUCHROMATIN

Low-density (as defined by electron microscopy) regions in the nucleus that are thought to contain open chromatin structures associated with the active transcription of genes.

HETEROCHROMATIN

High-density regions in the nucleus that are thought to contain compacted chromatin structures associated with silent genes.

DNASE-I-HYPERSENSITIVITY SITES

(DH sites). Areas of the genome that are thought to have an open chromatin configuration and are, therefore, accessible to DNase I.

EPIGENETIC

Any heritable influence (in the progeny of cells or of individuals) on chromosome or gene function that is not accompanied by a change in DNA sequence. Examples of epigenetic events include mammalian X-chromosome inactivation, imprinting, centromere inactivation and position effect variegation.

HISTONE DEACETYLASE

(HDAC). An enzyme that removes acetyl groups from histone tails.

HISTONE ACETYLTRANSFERASE

(HAT). An enzyme that adds acetyl groups to histone tails.

SILENCERS

DNA elements that repress promoter and/or enhancer activity in a position- and orientation-independent manner, possibly by influencing chromatin structure.

POSITION EFECT VARIEGATION

(PEV). A phenomenon in which a gene is activated in only a proportion of cells in the lineage in which it is normally expressed, owing to the proximity of heterochromatin.

LOCUS CONTROL REGION

(LCR). A gene-regulatory element that allows position-independent, copy-number-dependent and tissue-specific expression of transgenes.

CRE RECOMBINASE

Cre is a site-specific recombinase that recognizes and binds specific sites known as loxP. Two loxP sites recombine in the presence of Cre, allowing DNA that is cloned between two such sites to be removed by Cre-mediated recombination.

MATRIX-ATTACHMENT REGIONS

(MARs). DNA elements that are thought to tether loops of chromatin to specific sites in the nucleoplasm.

DNA METHYLTRANSFERASE 1

(DNMT1). An enzyme that maintains the methylation state of DNA during replication.

SATB1

(special AT-rich binding protein 1). A nuclear protein that recognizes double-stranded DNA with a high base-unpairing propensity and associates with matrix-attachment regions.

HIGH-MOBILITY GROUP BOX

(HMG box). A protein domain (found in many proteins of this family) that binds DNA and causes bending of its backbone.

BAF

(BRG- or hBRM-associated factor complex). One of several SWI/SNF-like chromatin-remodelling complexes in mammals.

SWI/SNF COMPLEX

A chromatin-remodelling multiprotein complex that was identified initially in yeast. Related complexes exist in mammals and are involved in remodelling the chromatin of various genes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kioussis, D., Ellmeier, W. Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Nat Rev Immunol 2, 909–919 (2002). https://doi.org/10.1038/nri952

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri952

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing