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

Baumann, M; Mamais, A; McBlane, F; Xiao, H; Boyes, J; (2003) Regulation of V(D)J recombination by nucleosome positioning at recombination signal sequences. EMBO J , 22 (19) 5197 - 5207.

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Abstract

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.

Type: Article
Title: Regulation of V(D)J recombination by nucleosome positioning at recombination signal sequences
Keywords: chromatin remodelling, chromosomal translocation, nucleosome positioning, RAGs, V(D)J recombination, HISTONE ACETYLATION, CHROMATIN STRUCTURE, IN-VITRO, DNA, PROMOTER, CLEAVAGE, GENE, TRANSCRIPTION, RECEPTOR, ACCESSIBILITY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/104583
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