Epigenetic Inheritance Research Articles

Paternal Inheritance Is an Important, but Overlooked, Factor Affecting the Adverse Effects of Microplastics and Nanoplastics on Subsequent Generations.

Microplastics (MPs) and nanoplastics (NPs) are widely detected in food and the human environment. More studies have begun to pay attention to the influence of MPs and NPs on genetics; in particular, exposure of paternal generation to MPs and NPs on epigenetic inheritance and the offspring of animal models have attracted considerable interest. In this Viewpoint, we mainly discuss the suggestion that reproductive genetic changes in the male parent have the potential to be transferred to the offspring and illustrate how MPs and NPs in the father tissues are distributed in later generations. We provide a systematic understanding of the potential health hazards of paternal exposure to MPs and NPs to subsequent generations and put forth recommendations about the epigenetic effects for future research on public health and food safety.

Aging affects gene expression in spermatids of Brown Norway rats

The effects of aging on the reproductive health of men and the consequences for their offspring are becoming more widely recognized. Correlative epidemiological studies examining paternal age and offspring health suggest there are more frequent occurrences of genetic disorders in the children of older fathers. Given the genetic basis for paternal age-related disorders, we aim to characterize gene expression in developing germ cells. Round spermatids (RS) were collected from young (mean = 5.3 months) and aged (mean = 19.5 months) Brown Norway rats, representative of humans aged 20–30 years and 55+ years, respectively. Gene expression data were obtained by mRNA sequencing (n = 5), and were analysed for differential expression. Sequencing data display 211 upregulated and 9 downregulated transcripts in RS of aged rats, compared to young (log2FC >1, p < 0.05). Transcripts with increased expression are involved in several processes including sperm motility/morphology, sperm-egg binding, capacitation, and epigenetic inheritance. In addition, there are numerous dysregulated transcripts that regulate germ cell epigenetic marks and Sertoli-germ cell binding and communication. These results show an overall increase in RS gene expression with age, with spermatogenic functions being perturbed. Taken together, these findings help identify the genetic origin of the fertility, germ cell niche, and epigenetic effects observed with advanced paternal aging.

I4mC-CPXG: A Computational Model for Identifying DNA N4- methylcytosine Sites in Rosaceae Genome Using Novel Encoding Strategy

Background: N4-methylcytosine (4mC) is one of the most widespread DNA methylation modifications, which plays an important role in DNA replication and repair, epigenetic inheritance, gene expression levels and regulation of transcription. Although biological experiments can identify potential 4mC modification sites, they are limited due to the experimental environment and labor intensive. Therefore, it is crucial to construct a computational model to identify the 4mC sites. background: N4-methylcytosine (4mC) is one of the most widespread DNA methylation modifications, which plays an important role in DNA replication and repair, epigenetic inheritance, gene expression levels and regulation of transcription. Although biological experiment can identify potential 4mC modification sites, it’s limited due to the experimental environment and labor intensive. Therefore, it is crucial to construct a computational model to identify the 4mC sites. Objective: Although some computational methods have been proposed to identify the 4mC sites, some problems should not be ignored, such as: (1) a large number of unknown nucleotides exist in the biological sequence; (2) a large number of zeros exist in the previous encoding technologies; (3) sequence distribution information is important to identify 4mC sites. Considering these aspects, we propose a computational model based on a novel encoding strategy with position specific information to identify 4mC sites. Methods: We constructed an accurate computational model i4mC-CPXG based on extreme gradient boosting. Two aspects of feature vectors are extracted according to nucleotide information and position specific information. From the aspect of nucleotide information, we used prior information to identify the base type of unknown nucleotide and decrease the influence of invalid information caused by lots of zeros. From the aspect of position specific information, the vector was designed carefully to express the base distribution and arrangement. Then the feature vector fused by nucleotide information and position specific information was input into extreme gradient boosting to construct the model. method: We constructed an accurate computational model i4mC-CPXG based on extreme gradient boosting. Two aspects feature vectors are extracted according to nucleotide information and position specific information. From the aspect of nucleotide information, we used prior information to identify the base type of unknown nucleotide and decrease the influence of invalid information caused by lots of zeros. From the aspect of position specific information, the vector was designed carefully to express the base distribution and arrangement. Then the feature vector fused by nucleotide information and position specific information was input into extreme gradient boosting to construct model. Results: The accuracy of i4mC-CPXG is 82.49% on independent dataset. The result was better than model i4mC-w2vec which was the best model in the imbalanced dataset with the ratio of 1:15. Meanwhile, our model achieved good performance on other species. These results validated the effectiveness of i4mC-CPXG. Conclusion: Our method is effective to identify potential 4mC modification sites due to the proposed new encoding strategy fused position specific information. The satisfactory prediction results of balanced datasets, imbalanced datasets and other species datasets indicate that i4mC-CPXG is valuable to provide a reasonable supplement for biology research. other: The satisfactory prediction results of balanced datasets, imbalanced datasets and other species datasets indicate that i4mC-CPXG is valuable to provide a reasonable supplement for biology research.

Epigenetic control of heredity.

Epigenetics is the field of science that deals with the study of changes in gene function that do not involve changes in DNA sequence and are heritable while epigenetics inheritance is the process of transmission of epigenetic modifications to the next generation. It can be transient, intergenerational, or transgenerational. There are various epigenetic modifications involving mechanisms such as DNA methylation, histone modification, and noncoding RNA expression, all of which are inheritable. In this chapter, we summarize the information on epigenetic inheritance, its mechanism, inheritance studies on various organisms, factors affecting epigenetic modifications and their inheritance, and the role of epigenetic inheritance in the heritability of diseases.

Epigenetic inheritance of gene silencing is maintained by a self-tuning mechanism based on resource competition

Biological systems can maintain memories over long timescales, with examples including memories in the brain and immune system. It is unknown how functional properties of memory systems, such as memory persistence, can be established by biological circuits. To address this question, we focus on transgenerational epigenetic inheritance in Caenorhabditis elegans. In response to a trigger, worms silence a target gene for multiple generations, resisting strong dilution due to growth and reproduction. Silencing may also be maintained indefinitely upon selection according to silencing levels. We show that these properties imply the fine-tuning of biochemical rates in which the silencing system is positioned near the transition to bistability. We demonstrate that this behavior is consistent with a generic mechanism based on competition for synthesis resources, which leads to self-organization around a critical state with broad silencing timescales. The theory makes distinct predictions and offers insights into the design principles of long-term memory systems.

Transgenerational Epigenetic Inheritance of Traumatic Experience in Mammals.

In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.

Epigenetic Inheritance and the Modern Evolutionary Synthesis

Epigenetic Inheritance and the Modern Evolutionary Synthesis

Abstract 1189: Transgenerational epigenetic inheritance of obesogenic traits in a C. elegans model

Abstract 1189: Transgenerational epigenetic inheritance of obesogenic traits in a C. elegans model

Applications of bioinformatics in epigenetics.

Epigenetic modifications such as DNA methylation, post-translational chromatin modifications and non-coding RNA-mediated mechanisms are responsible for epigenetic inheritance. Change in gene expression due to these epigenetic modifications are responsible for new traits in different organisms leading to various diseases including cancer, diabetic kidney disease (DKD), diabetic nephropathy (DN) and renal fibrosis. Bioinformatics is an effective approach for epigenomic profiling. These epigenomic data can be analyzed by a large number of bioinformatics tools and software. Many databases are available online, which comprises huge amount of information regarding these modifications. Recent methodologies include many sequencing and analytical techniques to extrapolate different types of epigenetic data. This data can be used to design drugs against diseases linked to epigenetic modifications. This chapter briefly highlights different epigenetics databases (MethDB, REBASE, Pubmeth, MethPrimerDB, Histone Database, ChromDB, MeInfoText database, EpimiR, Methylome DB, and dbHiMo), and tools (compEpiTools, CpGProD, MethBlAST, EpiExplorer, and BiQ analyzer), which are being utilized to retrieve the data and mechanistically analysis of epigenetics modifications.

Transgenerational inheritance and its modulation by environmental cues.

The epigenome plays an important role in shaping phenotypes. However, whether the environment can alter an organism's phenotype across several generations through epigenetic remodeling in the germline is still a highly debated topic. In this chapter, we briefly review the mechanisms of epigenetic inheritance and their connection with germline development before highlighting specific developmental windows of susceptibility to environmental cues. We further discuss the evidence of transgenerational inheritance to a range of different environmental cues, both epidemiological in humans and experimental in rodent models. Doing so, we pinpoint the current challenges in demonstrating transgenerational inheritance to environmental cues and offer insight in how recent technological advances may help deciphering the epigenetic mechanisms at play. Together, we draw a detailed picture of how our environment can influence our epigenomes, ultimately reshaping our phenotypes, in an extended theory of inheritance.

Multigenerational epigenetic inheritance in human: the past, present and perspectives

Nowadays, a growing body of evidence suggests that the developmental programs of each individual could be modified. The acquired new phenotypic changes could be persistent throughout the individual's life and even transmitted to the next generation. While the exact mechanism for that preservation is not well understood yet, there are many evidences showing that epigenetic alterations, which are robust and dynamic in response to the influence of the environmental factors, could be responsible for that inheritance. A growing number of external factors such as social stress, environmental pollution and climate changes make adaptation to these environmental changes rather challenging. According to the Developmental Origin of Human Disease theory, formulated by David Barker, environmental conditions experienced during the first phases of development can have long term effects on later phases of life. This phenomenon is linked to the biological plasticity of development, which allows reprogramming of physiological functions in response to different stimuli. Consequently, in utero exposure to environmental pollutants can increase predisposition to different pathologies that can occur both in early and later phases of life not only in the living generation but also in subsequent ones. Here, we have summarised some findings in human epigenetic research studies performed for the past few years which address the question whether transgenerational effects observed in model organisms could also occur in humans.

Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses

A great variety of endocrine-disrupting chemicals (EDCs) have been used extensively and become widespread in the environment nowadays. Limited mammalian studies have shown that certain EDCs may target chromosome and epigenome of the germline, leading to adverse effects in subsequent generations, despite these progenies having never been exposed to the EDC before. However, the underlying mechanisms of chromosomal changes induced by these pollutants remain poorly known. Using the human ovarian granulosa tumor cell line COV434 as a model, we investigated and compared the transcriptomic changes induced by nine EDCs with diverse chemical structures (i.e. BDE-47, BPA, BP-3, DEHP, DHP, EE2, TCS, TDCPP and NP), to inquire if there is any common epigenetic modification associated with reproductive functions induced by these EDCs. Our results showed that COV434 cells were more responsive to BP-3, NP, DEHP and EE2, and more importantly, these four EDCs altered the expression of gene clusters related to DNA damage response, cell cycle, proliferation, and chromatin remodeling, which can potentially lead to epigenetic modifications and transgenerational inheritance. Furthermore, dysregulation of similar gene clusters was common in DEHP and NP treatments. Bioinformatics analysis further revealed that BP-3 disturbed signaling pathways associated with reproductive functions, whereas alterations in telomere-related pathways were highlighted upon EE2 exposure. Overall, this study highlighted chromatin modifications caused by a class of chemicals which that may potentially lead to epigenetic changes and transgenerational reproductive impairments.

The Sperm Small RNA Transcriptome: Implications beyond Reproductive Disorder.

Apart from the paternal half of the genetic material, the male gamete carries assorted epigenetic marks for optimal fertilization and the developmental trajectory for the early embryo. Recent works showed dynamic changes in small noncoding RNA (sncRNA) in spermatozoa as they transit through the testicular environment to the epididymal segments. Studies demonstrated the changes to be mediated by epididymosomes during the transit through the adluminal duct in the epididymis, and the changes in sperm sncRNA content stemmed from environmental insults significantly altering the early embryo development and predisposing the offspring to metabolic disorders. Here, we review the current knowledge on the establishment of the sperm sncRNA transcriptome and their role in male-factor infertility, evidence of altered offspring health in response to the paternal life experiences through sperm sncRNA species and, finally, their implications in assisted reproductive technology in terms of epigenetic inheritance.

Examination of generational impacts of adolescent chemotherapy: Ifosfamide and potential for epigenetic transgenerational inheritance.

The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Pathologies such as delayed pubertal onset, kidney disease, and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) in chemotherapy lineage sperm in the F1 and F2 generations were identified. Therefore, chemotherapy exposure impacts pathology susceptibility in subsequent generations. Observations highlight the importance that prior to chemotherapy, individuals need to consider cryopreservation of germ cells as a precautionary measure if they have children.

Hypoxia induces transgenerational epigenetic inheritance of small RNAs

Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia-reared descendants are unclear. We show that hypoxia educes an intergenerational reduction in lipids and a transgenerational reduction in fertility in the nematode Caenorhabditis elegans. The transmission of these epigenetic phenotypes is dependent on repressive histone-modifying enzymes and the argonaute HRDE-1. Feeding naive C.elegans small RNAs extracted from hypoxia-treated worms is sufficient to induce a fertility defect. Furthermore, the endogenous small interfering RNA F44E5.4/5 is upregulated intergenerationally in response to hypoxia, and soaking naive normoxia-reared C.elegans with F44E5.4/5 double-stranded RNA (dsRNA) is sufficient to induce an intergenerational fertility defect. Finally, we demonstrate that labeled F44E5.4/5 dsRNA is itself transmitted from parents to children. Our results suggest that small RNAs respond to the environment and are sufficient to transmit non-genetic information from parents to their naive children.

The Epigenetic Control of the Transposable Element Life Cycle in Plant Genomes and Beyond.

Within the life cycle of a living organism, another life cycle exists for the selfish genome inhabitants, which are called transposable elements (TEs). These mobile sequences invade, duplicate, amplify, and diversify within a genome, increasing the genome's size and generating new mutations. Cells act to defend their genome, but rather than permanently destroying TEs, they use chromatin-level repression and epigenetic inheritance to silence TE activity. This level of silencing is ephemeral and reversible, leading to a dynamic equilibrium between TE suppression and reactivation within a host genome. The coexistence of the TE and host genome can also lead to the domestication of the TE to serve in host genome evolution and function. In this review, we describe the life cycle of a TE, with emphasis on how epigenetic regulation is harnessed to control TEs for host genome stability and innovation.

Parental mutations influence wild-type offspring via transcriptional adaptation.

Transgenerational epigenetic inheritance (TEI) is mostly discussed in the context of physiological or environmental factors. Here, we show intergenerational and transgenerational inheritance of transcriptional adaptation (TA), a process whereby mutant messenger RNA (mRNA) degradation affects gene expression, in nematodes and zebrafish. Wild-type offspring of animals heterozygous for mRNA-destabilizing alleles display increased expression of adapting genes. Notably, offspring of animals heterozygous for nontranscribing alleles do not display this response. Germline-specific mutations are sufficient to induce TA in wild-type offspring, indicating that, at least for some genes, mutations in somatic tissues are not necessary for this process. Microinjecting total RNA from germ cells of TA-displaying heterozygous zebrafish can trigger TA in wild-type embryos and in their progeny, suggesting a model whereby mutant mRNAs in the germline trigger a TA response that can be epigenetically inherited. In sum, this previously unidentified mode of TEI reveals a means by which parental mutations can modulate the offspring's transcriptome.

On the Role of Seminal Fluid Protein and Nucleic Acid Content in Paternal Epigenetic Inheritance

The evidence supports the occurrence of environmentally-induced paternal epigenetic inheritance that shapes the offspring phenotype in the absence of direct or indirect paternal care and clearly demonstrates that sperm epigenetics is one of the major actors mediating these paternal effects. However, in most animals, while sperm makes up only a small portion of the seminal fluid, males also have a complex mixture of proteins, peptides, different types of small noncoding RNAs, and cell-free DNA fragments in their ejaculate. These seminal fluid contents (Sfcs) are in close contact with the reproductive cells, tissues, organs, and other molecules of both males and females during reproduction. Moreover, their production and use are adjusted in response to environmental conditions, making them potential markers of environmentally- and developmentally-induced paternal effects on the next generation(s). Although there is some intriguing evidence for Sfc-mediated paternal effects, the underlying molecular mechanisms remain poorly defined. In this review, the current evidence regarding the links between seminal fluid and environmental paternal effects and the potential pathways and mechanisms that seminal fluid may follow in mediating paternal epigenetic inheritance are discussed.

Adaptation of Helicoverpa armigera to Soybean Peptidase Inhibitors Is Associated with the Transgenerational Upregulation of Serine Peptidases.

Molecular phenotypes induced by environmental stimuli can be transmitted to offspring through epigenetic inheritance. Using transcriptome profiling, we show that the adaptation of Helicoverpa armigera larvae to soybean peptidase inhibitors (SPIs) is associated with large-scale gene expression changes including the upregulation of genes encoding serine peptidases in the digestive system. Furthermore, approximately 60% of the gene expression changes induced by SPIs persisted in the next generation of larvae fed on SPI-free diets including genes encoding regulatory, oxidoreductase, and protease functions. To investigate the role of epigenetic mechanisms in regulating SPI adaptation, the methylome of the digestive system of first-generation larvae (fed on a diet with and without SPIs) and of the progeny of larvae exposed to SPIs were characterized. A comparative analysis between RNA-seq and Methyl-seq data did not show a direct relationship between differentially methylated and differentially expressed genes, while trypsin and chymotrypsin genes were unmethylated in all treatments. Rather, DNA methylation potential epialleles were associated with transcriptional and translational controls; these may play a regulatory role in the adaptation of H. armigera to SPIs. Altogether, our findings provided insight into the mechanisms of insect adaptation to plant antiherbivore defense proteins and illustrated how large-scale transcriptional reprograming of insect genes can be transmitted across generations.

Genetics, epigenetics and transgenerational transmission of obesity in children.

Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician's bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.