Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):1904-1909. doi: 10.1073/pnas.1615727114. Epub 2017 Feb 7.

H3K4me3 induces allosteric conformational changes in the DNA-binding and catalytic regions of the V(D)J recombinase.

Author information

1
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
2
Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
3
McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
4
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
5
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; sdesider@jhmi.edu.

Abstract

V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 stimulates substrate binding and catalysis, which are functions of RAG-1. This has suggested an allosteric mechanism in which information regarding occupancy of the RAG-2 PHD is transmitted to RAG-1. To determine whether the conformational distribution of RAG is altered by H3K4me3, we mapped changes in solvent accessibility of cysteine thiols by differential isotopic chemical footprinting. Binding of H3K4me3 to the RAG-2 PHD induces conformational changes in RAG-1 within a DNA-binding domain and in the ZnH2 domain, which acts as a scaffold for the catalytic center. Thus, engagement of H3K4me3 by the RAG-2 PHD is associated with dynamic conformational changes in RAG-1, consistent with allosteric control by active chromatin.

KEYWORDS:

DNA recombination; allosteric control; epigenetic modification; genomic plasticity; immune development

PMID:
28174273
PMCID:
PMC5338453
DOI:
10.1073/pnas.1615727114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center