Disruption of histone methylation in developing sperm impairs offspring health transgenerationally

Siklenka, Keith; Erkek, Serap; Godmann, Maren; Lambrot, Romain; McGraw, Serge; Lafleur, Christine; Cohen, Tamara; Xia, Jianguo; Suderman, Matthew; Hallett, Michael; Trasler, Jacquetta M.; Peters, Antoine H.F.M.; Kimmins, Sarah

doi:10.1126/science.aab2006

Cited by 465 publications

(392 citation statements)

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“…Epigenetic modulations encompass covalent chemical modifications of DNA (Razin & Riggs, 1980) and histone (Strahl & Allis, 2000) as well as the production of non-coding RNAs such as small interfering RNA (siRNA), microRNA (miRNA), Piwi-interacting RNA (piRNA), and transfer RNA (tRNA) fragments (Bartel, 2004;Flanagan & Wild, 2007;Mohammad et al, 2012;Chen et al, 2016;Sharma et al, 2016). Increasing evidence suggests that certain epigenetic changes, such as DNA methylation (Morgan et al, 1999;Rakyan et al, 2003;Carone et al, 2010;Franklin et al, 2010;Padmanabhan et al, 2013;Radford et al, 2014;Wei et al, 2014), histone modification (Katz et al, 2009;Greer et al, 2011;Seong et al, 2011;Ost et al, 2014;Siklenka et al, 2015), siRNA (Rechavi et al, 2011(Rechavi et al, , 2014Conine et al, 2013;HouriZe'evi et al, 2016), miRNAs (Gapp et al, 2014;Rodgers et al, 2015;He et al, 2016), piRNA (Ashe et al, 2012), and tRNA fragments Sharma et al, 2016) (Table 1) can be transmitted from parents to their offspring through the germline. Thus, the inheritance of epigenetic states may allow organisms to deliver either adaptive or non-adaptive/pathological information related to the ancestral environment to their offspring.…”

Section: Introductionmentioning

confidence: 99%

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

2017

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Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism. In certain circumstances, these effects can be transmitted across several generations through epigenetic (i.e. non-DNA sequence-based rather than mutational) modifications. In this review, we summarize recent evidence on epigenetic inheritance from parental environment-induced developmental and physiological alterations in nematodes, fruit flies, zebrafish, rodents, and humans. The epigenetic modifications demonstrated to be both susceptible to modulation by environmental cues and heritable, including DNA methylation, histone modification, and small non-coding RNAs, are also summarized. We particularly focus on evidence that parental environment-induced epigenetic alterations are transmitted through both the maternal and paternal germlines and exert sex-specific effects. The thought-provoking data presented here raise fundamental questions about the mechanisms responsible for these phenomena. In particular, the means that define the specificity of the response to parental experience in the gamete epigenome and that direct the establishment of the specific epigenetic change in the developing embryos, as well as in specific tissues in the descendants, remain obscure and require elucidation. More precise epigenetic assessment at both the genome-wide level and single-cell resolution as well as strategies for breeding at relatively sensitive periods of development and manipulation aimed at specific epigenetic modification are imperative for identifying parental environment-induced epigenetic marks across generations. Considering their diverse epigenetic architectures, the conservation and prevalence of the mechanisms underlying epigenetic inheritance in non-mammals require further investigation in mammals. Interpretation of the consequences arising from epigenetic inheritance on organisms and a better understanding of the underlying mechanisms will provide insight into how gene-environment interactions shape developmental processes and physiological functions, which in turn may have wide-ranging implications for human health, and understanding biological adaptation and evolution.

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Section: Introductionmentioning

confidence: 99%

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

2017

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“…Another piece of evidence corroborating the role for histones in transgenerational inheritance came from the work that showed sperm to be epigenetically programmed to regulate the transcription of several embryonic genes (30). The disruption of histone methylation in the developing sperm impairs the health of the offspring (31). Taken together, these findings raise the possibility that histone marks, which are retained in sperm, play a key role in safekeeping epigenetic information for subsequent generations.…”

Section: Introductionmentioning

confidence: 99%

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

et al. 2016

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The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.

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“…information directed by maternal and/or paternal instruction (44,45). How this information is transduced to affect gene expression in response to a given stimulus is currently speculative at best.…”

Section: N="normal"mentioning

confidence: 99%

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

Demoinet

Roy

2017

Proc. Natl. Acad. Sci. U.S.A.

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Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner. We show here that during periods of acute starvation in Caenorhabditis elegans larvae, the master metabolic regulator AMP-activated protein kinase (AMPK) plays a critical role in blocking modifications to the chromatin landscape. This ensures that gene expression remains inactive in the germ-line precursors during adverse conditions. In its absence, critical chromatin modifications occur in the primordial germ cells (PGCs) of emergent starved L1 larvae that correlate with compromised reproductive fitness of the generation that experienced the stress, but also in the subsequent generations that never experienced the initial event. Our findings suggest that AMPK regulates the activity of the chromatin modifying COMPASS complex (complex proteins associated with Set1) to ensure that chromatin marks are not established until nutrient/energy contingencies are satisfied. Our study provides molecular insight that links metabolic adaptation to transgenerational epigenetic modification in response to acute periods of starvation.epigenetics | AMPK | histone methyltransferase | COMPASS | C. elegans

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Disruption of histone methylation in developing sperm impairs offspring health transgenerationally

Cited by 465 publications

References 63 publications

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

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