Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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Testing for a role of Dnmt2 in paternal trans-generational immune priming

10.1101/422063 ◽

2018 ◽

Cited By ~ 2

Author(s):

Nora K E Schulz ◽

Maike F Diddens-de Buhr ◽

Joachim Kurtz

Keyword(s):

Potential Role ◽

Epigenetic Inheritance ◽

Red Flour Beetle ◽

Adult Offspring ◽

Paternal Effects ◽

Immune Priming ◽

Transgenerational Epigenetic Inheritance ◽

Generational Effects ◽

Underlying Mechanisms

AbstractTrans-generational effects from fathers to offspring are increasingly reported from diverse organisms, but the underlying mechanisms are often unknown. Paternal trans-generational immune priming (TGIP) was demonstrated in the red flour beetle Tribolium castaneum: non-infectious bacterial exposure (priming) of fathers protects their offspring against an infectious challenge. Here we studied a potential role of the Dnmt2 (now also called Trdnmt1) gene, which encodes a highly conserved enzyme that provides CpG methylation to a set of tRNAs and has previously been reported to be involved in transgenerational epigenetic inheritance in mice. We first studied gene expression and found that Dnmt2 was expressed throughout life, with high expression in testes. Knockdown of Dnmt2 in fathers slowed down offspring larval development and increased mortality of the adult offspring upon bacterial infection. However, the observed effects were independent of the paternal priming treatment. In conclusion, our results point towards a role of Dnmt2 for paternal effects, while elucidation of the mechanisms behind paternal TGIP needs further studies.

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Do Transgenerational Epigenetic Inheritance and Immune System Development Share Common Epigenetic Processes?

Journal of Developmental Biology ◽

10.3390/jdb9020020 ◽

2021 ◽

Vol 9 (2) ◽

pp. 20

Author(s):

Rwik Sen ◽

Christopher Barnes

Keyword(s):

Immune Response ◽

Immune System ◽

System Development ◽

Epigenetic Inheritance ◽

Epigenetic Modifications ◽

Future Research ◽

Transgenerational Epigenetic Inheritance ◽

Immune System Development ◽

And Function

Epigenetic modifications regulate gene expression for development, immune response, disease, and other processes. A major role of epigenetics is to control the dynamics of chromatin structure, i.e., the condensed packaging of DNA around histone proteins in eukaryotic nuclei. Key epigenetic factors include enzymes for histone modifications and DNA methylation, non-coding RNAs, and prions. Epigenetic modifications are heritable but during embryonic development, most parental epigenetic marks are erased and reset. Interestingly, some epigenetic modifications, that may be resulting from immune response to stimuli, can escape remodeling and transmit to subsequent generations who are not exposed to those stimuli. This phenomenon is called transgenerational epigenetic inheritance if the epigenetic phenotype persists beyond the third generation in female germlines and second generation in male germlines. Although its primary function is likely immune response for survival, its role in the development and functioning of the immune system is not extensively explored, despite studies reporting transgenerational inheritance of stress-induced epigenetic modifications resulting in immune disorders. Hence, this review draws from studies on transgenerational epigenetic inheritance, immune system development and function, high-throughput epigenetics tools to study those phenomena, and relevant clinical trials, to focus on their significance and deeper understanding for future research, therapeutic developments, and various applications.

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Transgenerational epigenetic inheritance: resolving uncertainty and evolving biology

BioMolecular Concepts ◽

10.1515/bmc-2015-0005 ◽

2015 ◽

Vol 6 (2) ◽

pp. 87-103 ◽

Cited By ~ 15

Author(s):

Abhay Sharma

Keyword(s):

Epigenetic Inheritance ◽

Integrative Model ◽

Evolutionary Significance ◽

Information Propagation ◽

Transgenerational Inheritance ◽

Epigenetic Memory ◽

Transgenerational Epigenetic Inheritance ◽

Fundamental Challenge ◽

Experimental Findings

AbstractTransgenerational epigenetic inheritance in animals has increasingly been reported in recent years. Controversies, however, surround this unconventional mode of heredity, especially in mammals, for several reasons. First, its existence itself has been questioned due to perceived insufficiency of available evidence. Second, it potentially implies transfer of hereditary information from soma to germline, against the established principle in biology. Third, it inherently requires survival of epigenetic memory across reprogramming, posing another fundamental challenge in biology. Fourth, evolutionary significance of epigenetic inheritance has also been under debate. This article pointwise addresses all these concerns on the basis of recent empirical, theoretical and conceptual advances. 1) Described here in detail are the key experimental findings demonstrating the occurrence of germline epigenetic inheritance in mammals. 2) Newly emerging evidence supporting soma to germline communication in transgenerational inheritance in mammals, and a role of exosome and extracellular microRNA in this transmission, is thoroughly discussed. 3) The plausibility of epigenetic information propagation across reprogramming is highlighted. 4) Analyses supporting evolutionary significance of epigenetic inheritance are briefly mentioned. Finally, an integrative model of ‘evolutionary transgenerational systems biology’ is proposed to provide a framework to guide future advancements in epigenetic inheritance.

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Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs

Cells ◽

10.3390/cells8091108 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1108 ◽

Cited By ~ 5

Author(s):

Karine Casier ◽

Antoine Boivin ◽

Clément Carré ◽

Laure Teysset

Keyword(s):

Small Rnas ◽

Epigenetic Inheritance ◽

Disease Development ◽

Epigenetic Mechanisms ◽

Transgenerational Inheritance ◽

Epigenetic Memory ◽

Transgenerational Epigenetic Inheritance ◽

Open Questions ◽

Sporadic Disease

Environmentally-induced transgenerational epigenetic inheritance is an emerging field. The understanding of associated epigenetic mechanisms is currently in progress with open questions still remaining. In this review, we present an overview of the knowledge of environmentally-induced transgenerational inheritance and associated epigenetic mechanisms, mainly in animals. The second part focuses on the role of PIWI-interacting RNAs (piRNAs), a class of small RNAs involved in the maintenance of the germline genome, in epigenetic memory to put into perspective cases of environmentally-induced transgenerational inheritance involving piRNA production. Finally, the last part addresses how genomes are facing production of new piRNAs, and from a broader perspective, how this process might have consequences on evolution and on sporadic disease development.

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