Deletion of germline promoter PDβ1 from the TCRβ locus causes hypermethylation that impairs Dβ1 recombination by multiple mechanisms

被引：77

作者：

Whitehurst, CE

Schlissel, MS

Chen, JZ ^{[1
]}

机构：

[1] MIT, Ctr Canc Res, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

来源：

IMMUNITY | 2000年 / 13卷 / 05期

关键词：

D O I：

10.1016/S1074-7613(00)00069-8

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The role of the germline transcriptional promoter, PD beta1, in V(D)J recombination at the T cell receptor beta locus was investigated. Deletion of PD beta1 caused reduced germline transcription and DNA hypermethylation in the D beta1-J beta1 region and decreased D beta1 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 beta1 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.

引用

页码：703 / 714

页数：12

共 47 条

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