Dataset Information


Proper chromatin programming during spermatogenesis is required for embryonic development

ABSTRACT: Epigenetic mechanisms including DNA methylation, non-coding RNAs and histone modifications control gene expression. Studies suggest that a father's lifetime experiences can be transmitted to his offspring to affect development and health. The mechanisms underlying such epigenetic inheritance are unknown. A potential route for paternal transmission is the unique chromatin composition of spermatozoa. Unlike somatic cells and oocytes, most nucleosomes in sperm are replaced with protamine nucleoproteins. The role of residual nucleosomes, residing at gene regulatory sequences, for epigenetic control of embryonic development is unknown. Here we generated a transgenic mouse model in which over-expression of the histone H3 lysine 4 (H3K4) demethylase LSD1/KDM1A during spermatogenesis alters H3K4 methylation in sperm. Strikingly, KDM1A over-expression in one generation causes severe embryonic defects in non-transgenic descendants spanning three subsequent generations. We show for the first time that correct histone methylation homeostasis during spermatogenesis is critical for offspring development and survival over multiple generations. Identification of H3K4me2 and nucleosome occupancies in sperm of wildtype mice, KDM1A transgenic mice and their non-transgenic littermates.

ORGANISM(S): Mus musculus  

SUBMITTER: Serap Erkek   Keith Siklenka  Sarah Kimmins  Antoine H Peters  Antoine Peters 

PROVIDER: E-GEOD-55471 | ArrayExpress | 2015-11-03



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Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.

Siklenka Keith K   Erkek Serap S   Godmann Maren M   Lambrot Romain R   McGraw Serge S   Lafleur Christine C   Cohen Tamara T   Xia Jianguo J   Suderman Matthew M   Hallett Michael M   Trasler Jacquetta J   Peters Antoine H F M AH   Kimmins Sarah S  

Science (New York, N.Y.) 20151008 6261

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 overexp  ...[more]

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