Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Paternally-induced transgenerational environmental reprogramming of metabolic gene expression in mammals (dye swap)

ABSTRACT: Epigenetic information can be inherited through the mammalian germline, and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet. Characterizing the RNA exression changes in livers of offspring mice in response to the paternal diet, comparing between low-protein diet and control-diet. Examination of the effect of 2 different paternal diets, control diet and low-protein diet, on the mRNA expression in the liver of the offsprinngs. 26 samples: including Control diet vs. Low-protein (with dye swap), and Control diet vs. Low-protein after fasting the mice.

ORGANISM(S): Mus musculus

SUBMITTER: naomi habib

PROVIDER: E-GEOD-25895 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.

Carone Benjamin R BR Fauquier Lucas L Habib Naomi N Shea Jeremy M JM Hart Caroline E CE Li Ruowang R Bock Christoph C Li Chengjian C Gu Hongcang H Zamore Phillip D PD Meissner Alexander A Weng Zhiping Z Hofmann Hans A HA Friedman Nir N Rando Oliver J OJ

Cell 20101201 7

Epigenetic information can be inherited through the mammalian germline and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet. Offspring of males fed a low-protein diet exhibited elevated hepatic expression of many genes involved in lipid and cholesterol biosynthesis and decreased ...[more]

PMID: 21183072

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Project description:Parental exposure to environmental stress can result in an increased diseases risk in the offspring. Although literature on maternal contribution to hereditary diseases are growing, the paternal contribution is frequently underrecognized. Since human studies reported that 80% of transmitted mutations arise in the paternal germline, it is crucial to understand the mechanism underlying the paternally inherited genome instability. Ionizing radiation (IR) is a major source of mutagenesis through inducing DNA double-strand breaks (DSBs). Here, we used sex-separated C. elegans mutants to investigate the paternal contribution to IR-induced transgenerational effects. Specifically, we found that paternal exposure to IR leads to a transgenerational embryonic lethality, and this effect is only observed when the radiation exposure occurred close to the time of fertilization. In the offspring of the irradiated males (F1 generation), we detected various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement, and aneuploidy. These phenotypes are attributed to the usage of two error-prone repair machinery, the polymerase-theta mediated end joining (TMEJ) and the non-homologous End Joining (NHEJ). Surprisingly, depletion of a human histone H1.0 ortholog, HIS-24, can significantly rescue this transgenerational embryonic lethality. Moreover, this rescue effect is associated with the downregulation of heterochromatin marker histone 3 lysine 9 di-methylation (H3K9me2), and the knocking-down of heterochromatin protein, HPL-1, could mimic the rescue effect of HIS-24 depletion. We also noticed that removal of the histone H1 and heterochromatin marker could activate the error-free repair machinery, Homologous Recombination repair (HR), thus improving the viability of the offspring carrying paternally inherited DNA damage. Altogether, our work sheds light on the importance of paternal radiation exposure on the health of offspring. In addition, our work establishes a previously unknown mechanism underlying the transgenerational genome instability and provides a potential therapeutic target for preventing the hereditary diseases caused by paternal radiation exposure.

Dataset Information

Paternally-induced transgenerational environmental reprogramming of metabolic gene expression in mammals (dye swap)

Publications

Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.

Similar Datasets

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