Epigenetic, genetic and maternal effects enable stable centromere inheritance
Centromeres are defined epigenetically by the histone H3 variant CENP-A. The propagation cycle by which pre-existing CENP-A nucleosomes serve as templates for nascent assembly predicts the epigenetic memory of weakened centromeres. Using a mouse model with reduced levels of CENP-A nucleosomes, we fi...
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Published in | Nature cell biology Vol. 24; no. 5; pp. 748 - 756 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Nature Publishing Group
01.05.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Centromeres are defined epigenetically by the histone H3 variant CENP-A. The propagation cycle by which pre-existing CENP-A nucleosomes serve as templates for nascent assembly predicts the epigenetic memory of weakened centromeres. Using a mouse model with reduced levels of CENP-A nucleosomes, we find that an embryonic plastic phase precedes epigenetic memory through development. During this phase, nascent CENP-A nucleosome assembly depends on the maternal Cenpa genotype rather than the pre-existing template. Weakened centromeres are thus limited to a single generation, and parental epigenetic differences are eliminated by equal assembly on maternal and paternal centromeres. These differences persist, however, when the underlying DNA of parental centromeres differs in repeat abundance, as assembly during the plastic phase also depends on sufficient repetitive centromere DNA. With contributions of centromere DNA and the Cenpa maternal effect, we propose that centromere inheritance naturally minimizes fitness costs associated with weakened centromeres or epigenetic differences between parents. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Ar. D: Experiments, quantifications, data analysis and statistical analysis, animal husbandry, genotyping. A.I.O: Experiments and quantification for some of Fig. 3g. J.D.M: Preparing and characterizing new reagents and assisting with statistical analysis. As. D: Initial experimentation in zygotes and early embryos. K.G.B: animal husbandry. Ar. D., B.E.B. and M.A.L: Experimental design, data interpretation and writing. B.E.B. and M.A.L: Supervision and funding. Current address: Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa, Greece Current address: Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975W. Walnut St. Indianapolis IN, USA Author contributions |
ISSN: | 1465-7392 1476-4679 |
DOI: | 10.1038/s41556-022-00897-w |