Epigenetics at the Epicenter of Modern Medicine

Feinberg, Andrew P.

doi:10.1001/jama.299.11.1345

Cited by 358 publications

(323 citation statements)

References 36 publications

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“…The cell-level processes by which these conditional adaptations occur include changes in the expression of regulatory genes, such as developmental changes in the frequency of DNA methylation at specific CpG sites (65). These are epigenetic phenomena, that is, modification of the DNA or associated proteins, other than DNA sequence variation, that carry information during cell division (66). The same epigenetic processes, including but not limited to DNA methylation, are likely key mechanisms by which early environmental signals are transduced into conditionally adaptive changes in metabolic, endocrine, and neuroregulatory pathways.…”

Section: Deep Archeologymentioning

confidence: 99%

Putting the concept of biological embedding in historical perspective

Hertzman

2012

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

194

164

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This paper describes evidence that led to the concept of biological embedding and research approaches designed to elucidates its mechanisms. Biological embedding occurs when experience gets under the skin and alters human biological and developmental processes; when systematic differences in experience in different social environments in society lead to systematically different biological and developmental states; when these differences are stable and long term; and, finally, when they have the capacity to influence health, well-being, learning, or behavior over the life course. Biological embedding emerged from insights in population health on the unique characteristics of socioeconomic gradients: Ubiquity in poor and postscarcity societies alike; gradient seen regardless of whether socioeconomic status is measured by income, education, or occupation; cutting widely across health, well-being, learning, and behavior outcomes; replicating itself on new conditions entering society; and, often, showing that flatter gradients mean better overall societal outcomes. Most important, the gradient begins the life course as a gradient in developmental health, suggesting that the emergence of a multifaceted resilience/vulnerability early in life is the best place to look for evidence of biological embedding. To understand its character, the metaphor of the “archeology of biological embedding” has been used, wherein the surficial stratum of the “dig” is experience and behavior, the shallow stratum is organ system and cellular function, and the deep stratum is gene function. We are now ready to address the fundamental question of biological embedding: How do early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course?

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Section: Deep Archeologymentioning

confidence: 99%

Putting the concept of biological embedding in historical perspective

Hertzman

2012

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

194

164

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“…Addition of epigenetic data will help clarify the functional basis underlying such joint effects by providing unbiased biologic measures arising from the combined effects of such interactions (and stochastic effects) that may lead to altered gene activity. The common disease genetic and epigenetic model provides a starting framework for including epigenetic data in genetic studies (13,170).…”

Section: Considerations For Epidemiologic Studies Involving Epigenetimentioning

confidence: 99%

Prospects for Epigenetic Epidemiology

Foley¹,

Craig²,

Morley³

et al. 2008

American Journal of Epidemiology

220

162

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“…Histone acetylation patterns in somatic cells are dynamically balanced by histone acetyltransferase and HDAC activities in response to intrinsic or environmental signals. Moreover, as chromatin-associated marks, they potentially play a role in the maintenance or reestablishment of chromatin composition after mitosis and/or meiosis (Feinberg, 2008;Pray, 2008;Blevins et al, 2014). HDACs, which belong to a class of enzymes that is evolutionarily conserved from prokaryotes to eukaryotes (Gregoretti et al, 2004;Menegola et al, 2006), are important for both animal and plant physiology and development (Menegola et al, 2006;Hollender and Liu, 2008;Kucharski et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors

et al. 2015

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To secure their access to water, light, and nutrients, many plant species have developed allelopathic strategies to suppress competitors. To this end, they release into the rhizosphere phytotoxic substances that inhibit the germination and growth of neighbors. Despite the importance of allelopathy in shaping natural plant communities and for agricultural production, the underlying molecular mechanisms are largely unknown. Here, we report that allelochemicals derived from the common class of cyclic hydroxamic acid root exudates directly affect the chromatin-modifying machinery in Arabidopsis thaliana. These allelochemicals inhibit histone deacetylases both in vitro and in vivo and exert their activity through locus-specific alterations of histone acetylation and associated gene expression. Our multilevel analysis collectively shows how plant-plant interactions interfere with a fundamental cellular process, histone acetylation, by targeting an evolutionarily highly conserved class of enzymes.

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Epigenetics at the Epicenter of Modern Medicine

Cited by 358 publications

References 36 publications

Putting the concept of biological embedding in historical perspective

Putting the concept of biological embedding in historical perspective

Prospects for Epigenetic Epidemiology

Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors

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