Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination.
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.
Nightingale
Karl P
KP
Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Baumann
Matthias
M
Eberharter
Anton
A
Mamais
Adamantios
A
Becker
Peter B
PB
Boyes
Joan
J
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004330:Drosophila / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011995:Recombination, Genetic
D006657:Histones; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009707:Nucleosomes; C064658:RAG-1 protein