First Author | Whitehurst CE | Year | 2000 |
Journal | Immunity | Volume | 13 |
Issue | 5 | Pages | 703-14 |
PubMed ID | 11114382 | Mgi Jnum | J:66014 |
Mgi Id | MGI:1927725 | Doi | 10.1016/s1074-7613(00)00069-8 |
Citation | Whitehurst CE, et al. (2000) Deletion of germline promoter PDbeta1 from the TCRbeta locus causes hypermethylation that impairs dbeta1 recombination by multiple mechanisms. Immunity 13(5):703-14 |
abstractText | The role of the germline transcriptional promoter, PDbeta1, in V(D)J recombination at the T cell receptor beta locus was investigated. Deletion of PDbeta1 caused reduced germline transcription and DNA hypermethylation in the Dbeta1-Jbeta1 region and decreased Dbeta1 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' Dbeta1 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. |