Understanding transgenerational epigenetic inheritance via the gametes in mammals

Daxinger, Lucia; Whitelaw, Emma

doi:10.1038/nrg3188

Cited by 605 publications

(520 citation statements)

References 130 publications

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“…Since them, many evidences have been accumulated in the defence of this audacious postulate but only in the last few years there is more widespread acceptance of the theory. Although the molecular basis of this inheritance remains unclear, recent evidence points towards diffusible factors, in particular RNA, rather than DNA methylation or chromatin (Daxinger and Whitelaw, 2012). It seems that there are two crucial moments in which epigenetic information undergoes extensive reprogramming and becomes erased and reestablished: during gametogenesis and again in early embryogenesis, two events characterized by extensive changes in DNA methylation and chromatin modifications (Feng et al, 2010).…”

Section: Inheritance Of Epigenetic Traitsmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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Section: Inheritance Of Epigenetic Traitsmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

View full text Add to dashboard Cite

show abstract

“…Although there could be a role in GCC development and inheritance via aberrant piRNA regulation, the mechanisms and biology remain poorly understood. The role of RNAs in transgenerational inheritance is extensively reviewed elsewhere (Daxinger and Whitelaw, 2012, Jones and Liang, 2009, Rassoulzadegan and Cuzin, 2010.…”

Section: Epigenetic Memory and Inheritancementioning

confidence: 99%

Role of epigenetics in the etiology of germ cell cancer

Zwan¹,

Stoop²,

Rossello³

et al. 2013

Int. J. Dev. Biol.

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Embryonic development is strictly controlled by functionality of genes in which the existing networks can act both on transcription and translation regulation. Germ cell cancers (GCC) are unique because of a number of characteristics. In spite of their clinical presentation, i.e., predominantly after puberty, they arise from primordial germ cells/gonocytes that have failed appropriate maturation to either pre-spermatogonia or oogonia. GCC mimic embryonal development to a certain extent, including capacity for totipotency. This knowledge has allowed the identification of informative diagnostic markers, including OCT3/4 (POU5F1), SOX2 and SOX17. An additional marker is the overall demethylated status of the genome. Genetic mutations in GCC are rare, which is exceptional for solid cancers. Our hypothesis is that a disturbed epigenetic regulation (through combined interaction of genetic or environmental parameters; referred to as genvironment) affect embryonic germ cell development, resulting in delayed or blocked maturation, and potentially progression to GCC. In this respect, studies of patients with Disorders of Sex Development (DSD) have increased our knowledge significantly. Genvironmental influences can lead to retention of existence of embryonic germ cells, the first step in the pathogenesis of GCC, resulting into the precursor lesions gonadoblastoma or carcinoma in situ. Identification of epigenetic alterations could lead to better understanding these processes and development of specific markers for early detection, eventually leading to development of targeted treatment. This review describes an interactive model related to the role of epigenetics in GCC pathogenesis, focusing on DNA methylation, histone modifications, epigenetic memory and inheritance, as well as environmental factors.

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“…Acquired inheritance would depend on the interaction between germ cells and somatic cells in the organism, either directly between gonadal somatic cells and germ cells, or indirectly by hormonal signaling. In general, acquired inheritance (and not the intrinsic inheritance program) is referred to as transgenerational inheritance [6].…”

Section: Introductionmentioning

confidence: 99%

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

Gill

Erkek

Peters

2012

Current Opinion in Cell Biology

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At fertilization, fusion of two differentiated gametes forms the zygote that is capable of forming all of the varied cell lineages of an organism. It is widely thought that the acquisition of totipotency involves extensive epigenetic reprogramming of the germline state into an embryonic state. However, recent data argue that this reprogramming is incomplete and that substantial epigenetic information passes from one generation to the next. In this review we summarize the changes in chromatin states that take place during mammalian gametogenesis and examine the evidence that early mammalian embryogenesis may be affected by inheritance of epigenetic information from the parental generation.

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Understanding transgenerational epigenetic inheritance via the gametes in mammals

Cited by 605 publications

References 130 publications

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Role of epigenetics in the etiology of germ cell cancer

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

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