Targeted inhibition of V(D)J recombination by a histone methyltransferase.

Published

Journal Article

The tissue- and stage-specific assembly of antigen receptor genes by V(D)J recombination is regulated by changes in the chromatin accessibility of target gene segments. This dynamic remodeling process is coordinated by cis-acting promoters and enhancers, which function as accessibility control elements. The basic epigenetic mechanisms that activate or repress chromatin accessibility to V(D)J recombinase remain unclear. We now demonstrate that a histone methyltransferase overrides accessibility control element function and cripples V(D)J recombination of chromosomal gene segments. The recruited histone methyltransferase induces extensive revisions in the local chromatin environment, including altered histone modifications and de novo methylation of DNA. These findings indicate a key function for histone methyltransferases in the tissue- and stage-specific suppression of antigen receptor gene assembly during lymphocyte development.

Full Text

Duke Authors

Cited Authors

  • Osipovich, O; Milley, R; Meade, A; Tachibana, M; Shinkai, Y; Krangel, MS; Oltz, EM

Published Date

  • March 2004

Published In

Volume / Issue

  • 5 / 3

Start / End Page

  • 309 - 316

PubMed ID

  • 14985714

Pubmed Central ID

  • 14985714

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1042

Language

  • eng

Conference Location

  • United States