An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation

17Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

V(D)J recombination is initiated by a specialized transposase consisting of the subunits RAG-1 and RAG-2. The susceptibility of gene segments to DNA cleavage by the V(D)J recombinase is correlated with epigenetic modifications characteristic of active chromatin, including trimethylation of histone H3 onlysine 4 (H3K4me3). Engagement of H3K4me3 by aplant homeodomain (PHD) in RAG-2 promotes recombination invivo and stimulates DNA cleavage by RAG invitro. We now show that H3K4me3 acts allosterically at the PHD finger to relieve autoinhibition imposed by a separate domain within RAG-2. Disruption of this autoinhibitory domain was associated with constitutive increases in recombination frequency, DNA cleavage activity, substrate binding affinity, and catalytic rate, thus mimicking the stimulatory effects of H3K4me3. Our observations support a model in which allosteric control of RAG is enforced by an autoinhibitory domain whose action is relieved by engagement of active chromatin.

Cite

CITATION STYLE

APA

Lu, C., Ward, A., Bettridge, J., Liu, Y., & Desiderio, S. (2015). An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation. Cell Reports, 10(1), 29–38. https://doi.org/10.1016/j.celrep.2014.12.001

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free