Deletion of germline promoter PD beta 1 from the TCR beta locus causes hypermethylation that impairs D beta 1 recombination by multiple mechanisms.

Autor: Whitehurst CE; Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Schlissel MS, Chen J
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2000 Nov; Vol. 13 (5), pp. 703-14.
DOI: 10.1016/s1074-7613(00)00069-8
Abstrakt: The role of the germline transcriptional promoter, PD beta 1, in V(D)J recombination at the T cell receptor beta locus was investigated. Deletion of PD beta 1 caused reduced germline transcription and DNA hypermethylation in the Dbeta1-J beta 1 region and decreased D beta 1 rearrangement. Analyses of methylation levels surrounding recombination signal sequences (RSS) before, during, and after recombination revealed that under physiological conditions cleavage of hypomethylated alleles was preferred over hypermethylated alleles. Methylation of a specific CpG site within the heptamer of the 3' D beta 1 RSS was incompatible with cleavage by the V(D)J recombinase. These findings suggest that methylation can regulate V(D)J recombination both at a general level by influencing regional chromatin accessibility and specifically by blocking RSS recognition or cleavage by the V(D)J recombinase.
Databáze: MEDLINE