2021
DOI: 10.1186/s13072-021-00403-w
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Programmed suppression of oxidative phosphorylation and mitochondrial function by gestational alcohol exposure correlate with widespread increases in H3K9me2 that do not suppress transcription

Abstract: Background A critical question emerging in the field of developmental toxicology is whether alterations in chromatin structure induced by toxicant exposure control patterns of gene expression or, instead, are structural changes that are part of a nuclear stress response. Previously, we used a mouse model to conduct a three-way comparison between control offspring, alcohol-exposed but phenotypically normal animals, and alcohol-exposed offspring exhibiting craniofacial and central nervous system … Show more

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Cited by 5 publications
(11 citation statements)
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“…Gene Enrichment Analysis using IPA identified alterations in the pathways regulating oxidative phosphorylation, mitochondrial function, EIF2, and Sirtuin signaling (Figure 6C). We recently described dysfunction of a similar set of pathways in the brains of mice exposed to alcohol in utero , 50 suggesting maternal and paternal alcohol exposures may program similar outcomes. Consistent with our previous study, we identified altered expression of several mitochondrial‐expressed transcripts and nuclear genes encoding mitochondrial enzymes (Figure 6D).…”
Section: Resultsmentioning
confidence: 98%
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“…Gene Enrichment Analysis using IPA identified alterations in the pathways regulating oxidative phosphorylation, mitochondrial function, EIF2, and Sirtuin signaling (Figure 6C). We recently described dysfunction of a similar set of pathways in the brains of mice exposed to alcohol in utero , 50 suggesting maternal and paternal alcohol exposures may program similar outcomes. Consistent with our previous study, we identified altered expression of several mitochondrial‐expressed transcripts and nuclear genes encoding mitochondrial enzymes (Figure 6D).…”
Section: Resultsmentioning
confidence: 98%
“…Identifying alterations in the expression of genes regulating mitochondrial function and oxidative phosphorylation is intriguing, especially given that we recently identified this same signature in a maternal model of alcohol exposure. 50 Epigenetic influences on mitochondrial function are an emerging area of interest in addiction and cancer biology. 61,62 Importantly, mitochondrial genome enriched small RNAs (mitosRNAs) are present in sperm.…”
Section: Discussionmentioning
confidence: 99%
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“…We did not observe any alterations in these same genes in either male or female placenta derived from High-concentration sires. Finally, our previous studies examining alcohol-induced changes in epigenetic programming have identified altered expression of several mitochondrial-expressed transcripts and nuclear genes regulating oxidative phosphorylation and mammalian target of rapamycin (mTOR) signaling ( Chang et al, 2021 ; Thomas et al, 2021 ). Similar to these previous studies, we identify suppression of these same candidate genes in placentae derived from the male and female offspring of Low-concentration sires but not the offspring of High-concentration males ( Figure 8D ).…”
Section: Resultsmentioning
confidence: 99%
“…In worms, these changes alter chromatin structure, specifically histone H3, lysine four trimethylation (H3K4me3) in both the soma and the germline, enabling the transgenerational propagation of an adaptive state (Tauffenberger and Parker, 2014;Kishimoto et al, 2017). We have observed suppression of pathways regulating oxidative phosphorylation in a high-dose model of early gestational EtOH exposure and recently identified this same signature in male placentae sired by EtOH-exposed fathers (Chang et al, 2021;Thomas et al, 2021). Further, we have identified alcohol-induced increases in H3K4me3 in alcoholexposed sperm (Bedi et al, 2022).…”
Section: Discussionmentioning
confidence: 95%