JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress.

Autor: Myers TR; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark.; Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark., Amendola PG; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark.; Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark., Lussi YC; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark.; Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark., Salcini AE; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark. lisa.salcini@bric.ku.dk.; Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark. lisa.salcini@bric.ku.dk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Feb 28; Vol. 8 (1), pp. 3765. Date of Electronic Publication: 2018 Feb 28.
DOI: 10.1038/s41598-018-21914-9
Abstrakt: Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells. Loss of jmjd-1.2 is not associated with major defects in the germ cells in animals grown under normal conditions or after DNA damage induced by UV or ionizing irradiation. However, jmjd-1.2 mutants are more sensitive to replication stress and the progeny of mutant animals exposed to hydroxyurea show increased embryonic lethality and mutational rate, compared to wild-type. Thus, our results suggest a role for jmjd-1.2 in the maintenance of genome integrity after replication stress and emphasize the relevance of the regulation of histone methylation in genomic stability.
Databáze: MEDLINE