Transcriptomics,Genomics

Dataset Information

46

Disruption of histone methylation in developing sperm impairs offspring health transgenerationally [embryo]


ABSTRACT: 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. Overall design: Identification of the RNA population in 2-cell embryos sired by wildtype mice, KDM1A transgenic mice and their non-transgenic littermates to C57BL/6 control females using gene expression array.

INSTRUMENT(S): [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]

SUBMITTER: Sarah Kimmins  

PROVIDER: GSE66051 | GEO | 2015-10-08

SECONDARY ACCESSION(S): PRJNA275781

REPOSITORIES: GEO

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Publications

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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