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Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination

Nightingale, KP; Baumann, M; Eberharter, A; Mamais, A; Becker, PB; Boyes, J; (2007) Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination. NUCLEIC ACIDS RES , 35 (18) 6311 - 6321. 10.1093/nar/gkm650. Gold open access

Abstract

Targeted chromatin remodelling is essential for many nuclear processes, including the regulation of V(D)J recombination. ATP-dependent nucleosome remodelling complexes are important players in this process whose activity must be tightly regulated. We show here that histone acetylation regulates nucleosome remodelling complex activity to boost RAG cutting during the initiation of V(D)J recombination. RAG cutting requires nucleosome mobilization from recombination signal sequences. Histone acetylation does not stimulate nucleosome mobilization per se by CHRAC, ACF or their catalytic subunit, ISWI. Instead, we find the more open structure of acetylated chromatin regulates the ability of nucleosome remodelling complexes to access their nucleosome templates. We also find that bromodomain/acetylated histone tail interactions can contribute to this targeting at limited concentrations of remodelling complex. We therefore propose that the changes in higher order chromatin structure associated with histone acetylation contribute to the correct targeting of nucleosome remodelling complexes and this is a novel way in which histone acetylation can modulate remodelling complex activity.

Type: Article
Title: Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination
Open access status: An open access publication
DOI: 10.1093/nar/gkm650
Keywords: TCR-GAMMA-LOCUS, HISTONE ACETYLATION, ORDERED RECRUITMENT, CHROMATIN-STRUCTURE, ISWI, TRANSCRIPTION, PROMOTER, CLEAVAGE, DNA, SWI/SNF
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/67661
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