Dynamic repositioning of CD4 and CD8 genes during T cell development

被引:26
作者
Delaire, S [1 ]
Huang, YH [1 ]
Chan, SW [1 ]
Robey, EA [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
关键词
lineage commitment; heterochromatin; positive selection; gene repression; nuclear position;
D O I
10.1084/jem.20041041
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although stable repression of CD4 and CD8 genes is a central feature of T cell lineage commitment, we lack detailed information about the timing and mechanism of this repression. Stable gene repression has been linked to the position of genes within the nucleus. Therefore, information about the nuclear position of CD4 and CD8 genes during T cell development could provide insights into both the mechanism of regulation of CD4 and CD8 genes, and the process of lineage commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes is associated with the repositioning of alleles close to heterochromatin. We also provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin can occur as an early response to positive selection signals. We discuss our results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4 versus CD8 lineage commitment.
引用
收藏
页码:1427 / 1435
页数:9
相关论文
共 51 条
[1]   A HUMAN CD4 TRANSGENE RESCUES CD4-CD8+ CELLS IN BETA-2-MICROGLOBULIN-DEFICIENT MICE [J].
BARON, A ;
HAFEN, K ;
VONBOEHMER, H .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (08) :1933-1936
[2]   Asynchronous coreceptor downregulation after positive thymic selection: Prolonged maintenance of the double positive state in CD8 lineage differentiation due to sustained biosynthesis of the CD4 coreceptor [J].
Barthlott, T ;
Kohler, H ;
Eichmann, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (02) :357-362
[3]   The CD4/CD8 lineage decision: integration of signalling pathways [J].
Basson, MA ;
Zamoyska, R .
IMMUNOLOGY TODAY, 2000, 21 (10) :509-514
[4]   Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division [J].
Brown, KE ;
Baxter, J ;
Graf, D ;
Merkenschlager, M ;
Fisher, AG .
MOLECULAR CELL, 1999, 3 (02) :207-217
[5]   Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin [J].
Brown, KE ;
Guest, SS ;
Smale, ST ;
Hahm, K ;
Merkenschlager, M ;
Fisher, AG .
CELL, 1997, 91 (06) :845-854
[6]   CD8 coreceptor extinction in signaled CD4+ CD8+ thymocytes:: Coordinate roles for both transcriptional and posttranscriptional regulatory mechanisms in developing thymocytes [J].
Cibotti, R ;
Bhandoola, A ;
Guinter, TI ;
Sharrow, SO ;
Singer, A .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (11) :3852-3859
[7]  
Correia-Neves M, 2001, EUR J IMMUNOL, V31, P2583, DOI 10.1002/1521-4141(200109)31:9<2583::AID-IMMU2583>3.0.CO
[8]  
2-Z
[9]   EVIDENCE FOR A STOCHASTIC MECHANISM IN THE DIFFERENTIATION OF MATURE SUBSETS OF T-LYMPHOCYTES [J].
DAVIS, CB ;
KILLEEN, N ;
CROOKS, MEC ;
RAULET, D ;
LITTMAN, DR .
CELL, 1993, 73 (02) :237-247
[10]   Morpholino antisense oligonucleotide-mediated gene knockdown during thymocyte development reveals role for Runx3 transcription factor in CD4 silencing during development of CD4-/CD8+ thymocytes [J].
Ehlers, M ;
Laule-Kilian, K ;
Petter, M ;
Aldrian, CJ ;
Grueter, B ;
Würch, A ;
Yoshida, N ;
Watanabe, T ;
Satake, M ;
Steimle, V .
JOURNAL OF IMMUNOLOGY, 2003, 171 (07) :3594-3604