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| Status |
Public on Jul 16, 2014 |
| Title |
Perturbed adult sperm methylome after in utero undernutrition is associated with transmission of metabolic disease |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
The pre and postnatal environment can affect both an individual’s risk of adult onset metabolic disease and that of subsequent generations. Although animal models and epidemiological data implicate epigenetic inheritance, little is known of the mechanisms involved. In a robust intergenerational model of developmental programming we demonstrate that the nutritional environment experienced in utero by F1 generation embryos alters the DNA methylome of the F1 adult male germ line in a locus-specific manner, without affecting overall methylation levels. Differentially methylated regions are mostly hypomethylated and are enriched in nucleosome retaining regions in adult sperm. A substantial fraction is resistant to early embryo methylation reprogramming, and thus have the potential to alter F2 generation development. Altered expression of transcripts neighbouring differentially methylated regions are evident in tissues of F2 offspring despite lack of persistence of differential methylation. Transmitted methylation variation in the germline at key regulatory loci may therefore contribute to the development of metabolic disease in the subsequent generation.
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| Overall design |
2 biological replicates of pooled sperm samples for each control (C) or undernutrition (UN) model
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| Contributor(s) |
Radford EJ, Ito M, Shi H, Corish J, Yamazawa K, Isganaitis E, Seisenberger S, Hore T, Reik W, Erkek S, Peters A, Patti M, Ferguson-Smith AC |
| Citation(s) |
25011554 |
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| Submission date |
Jun 23, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Hui Shi |
| E-mail(s) |
hs523@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
Department of Physiology, Development and Neuroscience
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| Street address |
Downing Street
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| City |
Cambridge |
| ZIP/Postal code |
CB2 3EG |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA253334 |
| SRA |
SRP043514 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58747_RAW.tar |
343.8 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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