| Literature DB >> 26449473 |
Keith Siklenka1, Serap Erkek2, Maren Godmann3, Romain Lambrot3, Serge McGraw4, Christine Lafleur3, Tamara Cohen3, Jianguo Xia5, Matthew Suderman6, Michael Hallett7, Jacquetta Trasler8, Antoine H F M Peters9, Sarah Kimmins10.
Abstract
A father's lifetime experiences can be transmitted to his offspring to affect health and development. However, the mechanisms underlying paternal epigenetic transmission are unclear. Unlike in 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 KDM1A (also known as LSD1) 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 germline 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.Entities:
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Year: 2015 PMID： 26449473 DOI： 10.1126/science.aab2006
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728