Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination.
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.
Collections
Subject
Cell Line
Nucleosomes
Animals
Drosophila
Immunoglobulin Joining Region
Immunoglobulin Variable Region
Homeodomain Proteins
Histones
Chromatin Assembly and Disassembly
Gene Rearrangement, B-Lymphocyte
Gene Rearrangement, T-Lymphocyte
Recombination, Genetic
Acetylation
Research team
Molecular Embryology
Language
eng
License start date
2007-01
Citation
Nucleic acids research, 2007, 35 (18), pp. 6311 - 6321