Epigenetics: A Landscape Takes Shape

Goldberg, Aaron D; Allis, C. David; Bernstein, Emily

doi:10.1016/j.cell.2007.02.006

Cited by 2,148 publications

(1,566 citation statements)

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“…Epigenetics in the current context refers to those mechanisms that lead to long-term changes in gene expression through chemical modification to or alterations in the packaging of DNA such that the capacity for transcriptional regulation is altered. 14 This may involve methylation of CpG sequences in the promoter regions of the gene or altered acetylation, methylation or ubiquitination of histones. These may be interlinkedF enhanced methylation may lead to or be induced by deacetylation of histones.…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

2008

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Although variation in individual lifestyle and genotype are important factors in explaining individual variation in the risk of developing obesity in an obesogenic environment, there is growing evidence that developmentally plastic processes also contribute. These effects are mediated at least in part through epigenetic processes. These developmental pathways do not directly cause obesity but rather alter the risk of an individual developing obesity later in life. At least two classes of developmental pathway are involved. The mismatch pathway involves the evolved adaptive responses of the developing organism to anticipated future adverse environments, which have maladaptive consequences if the environment is mismatched to that predicted. This pathway can be cued by prenatal undernutrition or stresses that lead the organism to forecast an adverse future environment and change its developmental trajectory accordingly. As a result, individuals develop with central and peripheral changes that increase their sensitivity to an obesogenic environment. It provides a model for how obesity emerges in populations in rapid transition, but also operates in developed countries. There is growing experimental evidence that this pathway can be manipulated by, for example, postnatal leptin exposure. Secondly, maternal diabetes, maternal obesity and infant overfeeding are associated with a greater risk of later obesity. Early life offers a potential point for preventative intervention.

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Section: Epigenetic Mechanismsmentioning

confidence: 99%

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

2008

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“…Strictly speaking, "epigenetics" refers to chromatin and DNA modifications that are heritable through cell division, but do not involve changes in the underlying DNA sequence [2]. However, since the aging process is not restricted to proliferating tissues and may, in fact, be influenced by irreversible proliferation arrest, we will use the term more loosely to refer to effects mediated by chromatin structure and DNA methylation, but not DNA sequence.…”

Section: Introductionmentioning

confidence: 99%

Aging by epigenetics—A consequence of chromatin damage?

Sedivy

Gowrishankar

Adams

2008

Experimental Cell Research

142

102

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Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

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“…Periconceptional parental lifestyle and epigenetic programming of offspring health after spontaneous conception During gametogenesis and early embryonic development several biological and lifestyle conditions (age, subfertility, nutrition, smoking, alcohol) can influence the epigenetic fetal programming introducing a number of heritable modifications in gene activity and expression that occur without alteration in DNA sequence [41]. Genomic imprinting operates to silence the maternal or paternal alleles of genes that often are organized in clusters.…”

Section: Congenital Malformationsmentioning

confidence: 99%

Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report

Albertini

Evers²,

Geraedts³

et al. 2014

J Assist Reprod Genet

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Purpose Assisted Reproduction Treatment (ART) is here to stay. This review addresses the parental background of birth defects, before, during and after conception and focuses both on the underlying subfertility and on the question whether ART as a treatment is an additional contributing factor. Methods Searches were performed in Medline and other databases. Summaries were discussed in a Delphi panel set-up by the European Society of Human Reproduction and Embryology (ESHRE). Results Several birth defects and adult diseases arise during the earliest stages of ovarian development and oocyte differentiation: this is the case of cleft palate disorders in offspring from female rat exposed to Dioxin during fetal life or the polycystic ovary diseases in female offspring (primates) exposed to elevated androgen concentration during fetal life. Human oocytes and embryos often fail to stop the propagation of aneuploid cells but maintain their ability to repair DNA damages including those introduced by the fertilizing sperm. There is a 29 % increased risk of birth defects in the newborns spontaneously conceived by subfertile couples and the risk is further increased (34 %) when conception is achieved by treating infertlity with ART (Danish IVF Registry). Periconceptional conditions are critical for ART babies: their birth weight is in general smaller (Norvegian Registry) but a more prolonged culture time doubled the number of large babies (Finnish Registry). Conclusion The long-term developmental effects of ART on child and subsequent health as an adult remains a subject worthy of futher monitoring and investigation. Capsule Remaining mindful of the growing body of evidence showing that during gamete production, genetic and epigenetic changes influence offspring health, serves to reinforce the need to continue to monitor ART children.

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Epigenetics: A Landscape Takes Shape

Abstract: Epigenetics has recently evolved from a collection of diverse phenomena to a defined and far-reaching field of study. In this Essay, we examine the epistemology of epigenetics, provide a brief overview of underlying molecular mechanisms, and suggest future challenges for the field.

Cited by 2,148 publications

References 20 publications

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

Aging by epigenetics—A consequence of chromatin damage?

Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report

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