Author: Siklenka K1, Erkek S2, Godmann M3, Lambrot R3, McGraw S4, Lafleur C3, Cohen T3, Xia J5, Suderman M6, Hallett M7, Trasler J8, Peters AH9, Kimmins S10
Affiliation: 1Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Canada. 2Friedrich Miescher Institute for Biomedical Research (FMI), CH-4058 Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. 3Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada. 4Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Canada. 5Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada. Institute of Parasitology, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada. 6MRC Integrative Epidemiology Unity, School of Social and Community Medicine, University of Bristol, Bristol, UK. 7McGill Centre for Bioinformatics, School of Computer Science, Faculty of Science, McGill University, Montreal, Canada. 8Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Canada. Departments of Human Genetics and Pharmacology & Therapeutics; Research Institute of the McGill University Health Centre at the Montreal Children's Hospital, Montreal, Canada. 9Friedrich Miescher Institute for Biomedical Research (FMI), CH-4058 Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. sarah.kimmins@mcgill.ca antoine.peters@fmi.ch. 10Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Canada. Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada. sarah.kimmins@mcgill.ca antoine.peters@fmi.ch.
Conference/Journal: Science
Date published: 2015 Oct 8
Other:
Pages: pii: aab2006 , Word Count: 138
A father's lifetime experiences can be transmitted to his offspring to affect health and development. The mechanisms underlying paternal epigenetic transmission are unclear. Unlike somatic cells, there are few nucleosomes in sperm and their function in epigenetic inheritance is unknown. We generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase LSD1/KDM1A during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring. These defects persisted transgenerationally in the absence of KDM1A germ line expression and were associated with altered RNA profiles in sperm and offspring. We show that epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions.
Copyright © 2015, American Association for the Advancement of Science.
PMID: 26449473