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  • The EMBO Journal (2003) 22, 5197 - 5207
  • doi:10.1093/emboj/cdg487

Regulation of V(D)J recombination by nucleosome positioning at recombination signal sequences

Matthias Baumann1, Adamantios Mamais1, Fraser McBlane2, Hua Xiao3 and Joan Boyes1

  1. Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
  2. European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy
  3. Laboratory of Molecular Cell Biology, National Cancer Institute, NIH Building 37, Room 6068, Bethesda, MD 20892, USA

Correspondence to:

Joan Boyes, E-mail: Joan.Boyes@icr.ac.uk

Received 9 January 2003; Accepted 5 August 2003; Revised 28 May 2003

A key component in the regulation of V(D)J recombination is control of the accessibility of RAG proteins to recombination signal sequences (RSS). Nucleosomes are known to inhibit this accessibility. We show here that the signal sequence itself represses accessibility by causing nucleosome positioning over the RSS. This positioning is mediated, in vitro and in vivo, by the conserved nonamer of the RSS. Consistent with this strong positioning, nucleosomes at RSSs are resistant to remodelling by nucleosome sliding. In vivo we find that consensus RSSs are preferentially protected, whereas those that lack a consensus nonamer, including some cryptic RSSs, fail to position nucleosomes. Decreased protection of these non-consensus RSSs correlates with their increased use in recombination assays. We therefore suggest that nucleosome positioning by RSSs provides a previously unanticipated level of protection and regulation of V(D)J recombination.

  • Keywords:

    • chromatin remodelling,
    • chromosomal translocation,
    • nucleosome positioning,
    • RAGs,
    • V(D)J recombination