Germ-line transcription and methylation status of the TCR-J alpha locus in its accessible configuration.
Eur J Immunol
; 27(7): 1619-25, 1997 Jul.
Article
em En
| MEDLINE
| ID: mdl-9247569
ABSTRACT
We have generated two in vivo mouse models to study the regulation of DNA accessibility to the V(D)J recombinase machinery in the T cell receptor (TCR)-J alpha locus. In recombination activating gene (RAG)-deficient mice, both injection of a TCR-beta chain transgene (RTB mice) or anti-CD3-epsilon treatment in vivo (RT3 mice) lead to the same phenotype with homogeneous thymocyte populations blocked at the CD4+ CD8+ double positive (DP) stage. At this developmental stage, the TCR-alpha rearrangements are about to start, and the TCR-J alpha locus is frozen in an accessible but yet unrearranged configuration in these mice. We show high level of TCR-alpha germ-line transcription in thymocytes from RTB and RT3 mice. Transcripts are skewed towards the 5' end of the TCR-J alpha locus, and the T early alpha (TEA) sterile transcript is predominant and therefore provides a useful marker for the TCR-J alpha locus opening. Analysis of the DNA methylation status reveals a global surmethylation of the TCR-J alpha locus in the thymus in comparison with non-lymphoid cells in these mice. We propose that hypermethylation of the locus could precede a progressive demethylation, providing a specific protective and regulatory role in the rearrangement events.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Rearranjo Gênico do Linfócito T
/
Receptores de Antígenos de Linfócitos T alfa-beta
/
Metilação de DNA
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
1997
Tipo de documento:
Article