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- JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability
JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability
Auteurs
Francisco Saavedra, Zachary A. Gurard-Levin, Camila Rojas-Villalobos, Isabelle Vassias, Raquel Quatrini, Geneviève Almouzni, Alejandra Loyola
Résumé
Abstract
Background
Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. Following their synthesis, histones undergo a series of maturation steps to prepare them for deposition onto chromatin.
Results
Here, we identify the lysine demethylase JMJD1B as a novel player in the maturation cascade that contributes to regulate histone provision. We find that depletion of JMJD1B increases the protein levels of the histone chaperone tNASP leading to an accumulation of newly synthesized histones H3 and H4 at early steps of the histone maturation cascade, which perturbs chromatin assembly. Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability.
Conclusions
Our data support a role for JMJD1B in fine-tuning histone supply to maintain genome integrity, opening novel avenues for cancer therapeutics.
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