The role of genomic imprinting in biology and disease: an expanding view

Peters, Jo

doi:10.1038/nrg3766

Cited by 401 publications

(373 citation statements)

References 159 publications

Supporting

Mentioning

336

Contrasting

Unclassified

Order By: Relevance

“…6 Imprinted genes play roles in development and have impact on human diseases, including obesity and cancer. 37 The differential gene expression is regulated by a short DNA sequence, the imprinting center region, which shows differential methylation. 38 Deletion of the imprinting center causes disruption of the parent-specific gene expression pattern.…”

Section: Resultsmentioning

confidence: 99%

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

et al. 2015

View full text Add to dashboard Cite

Several studies have described phenotypic changes in the offspring of mice exposed to a variety of environmental factors, including diet, toxins, and stress; however, the molecular pathways involved in these changes remain unclear. Using a high fat diet (HFD)-induced obesity mouse model, we examined liver gene expression in male offspring and analyzed chromatin of paternal spermatozoa. We found that the hepatic mRNA level of 7 genes (out of 20 evaluated) was significantly altered in HFD male offspring compared to control mice, suggesting that phenotypic changes in the offspring depend on parental diet. We examined 7 imprinted loci in spermatozoa DNA from HFD-treated and control fathers by bisulfite sequencing, but did not detect changes in DNA methylation associated with HFD. Using chromatin immunoprecipitation followed by high-throughput sequencing, we found differential histone H3-occupancy at genes involved in the regulation of embryogenesis and differential H3K4me1-enrichment at transcription regulatory genes in HFD fathers vs. control mice. These results suggest that dietary exposure can modulate histone composition at regulatory genes implicated in developmental processes.

show abstract

Section: Resultsmentioning

confidence: 99%

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Nevertheless, activation of normally silenced imprinted alleles can occur under naive conditions due to excessive demethylation, and once lost from an ICR, parent-specific methylation cannot be recovered [62]. Given that loss of imprinting is a known driver of developmental disease and cancer [64,65], its occurrence in naive cells would render them unsafe for clinical and transgenics applications. ICR erasure in primordial germ cells is thought to involve TET protein action [66][67][68][69], and as such, it is not unreasonable to expect that loss of imprinting in naive ESCs could be exacerbated by supplementation of vitamins A and C. This means that in order to strike a balance between imprinting fidelity in naive pluripotent stem cells and the efficiency at which they are derived, fine-tuning of vitamin levels and TET activity may be required …”

Section: Vitamins a And C In Regenerative Medicine And Mammalian Transgenmentioning

confidence: 99%

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Hore

2017

Epigenomics

View full text Add to dashboard Cite

Vitamins A and C represent unrelated sets of small molecules that are essential to the human diet and have recently been shown to intensify erasure of epigenetic memory in naive embryonic stem cells. These effects are driven by complementary enhancement of the ten-eleven translocation (TET) demethylases -vitamin A stimulates TET expression, whereas vitamin C potentiates TET catalytic activity. Vitamin A and C cosupplementation synergistically enhances reprogramming of differentiated cells to the naive state, but overuse may exaggerate instability of imprinted genes. As such, optimizing their use in culture media will be important for regenerative medicine and mammalian transgenics. In addition, mechanistic perception of how these vitamins interact with the epigenome may be relevant for understanding cancer and improving patient treatment. Figure 1A), and both are associated with a long recorded history. Nightblindness, an early symptom of vitamin A deficiency, and its cure through liver consumption, was known to Egyptians in the prehistoric period [1]. Equally, the debilitating effects of scurvy (vitamin C deficiency) among sailors, and its treatment with oranges, was registered as far back as 1498 [2]. Vitamins A and C also have a lengthy and rich history in scientific literature; in 1753 James Lind described the first controlled clinical trial where various antiscorbutic treatments were tested on British seamen and in 1929, Frederick Gowland Hopkins was co-awarded the Nobel Prize in Medicine for the 'discovery of vitamins' following milk supplementation experiments in vitamin A deficient mice [3]. Eventual isolation of the respective compounds underlying both vitamins led to Nobel Prizes in Chemistry and Medicine in 1937 [4]. Since this time, a considerable amount of scientific progress (and at times conjecture) has been associated with vitamins A and C, and their respective biological effects touch disciplines as divergent as development and dermatology.One of the most recently discovered fields that vitamins A and C impact upon is epigenetics [5][6][7]. New research has shown that both vitamins drive active removal of DNA methylation in embryonic stem cells (ESCs) by enhancing the same family of ten-eleven translocation (TET) enzymes, and in doing so, help erase DNA methylation and the epigenetic memory encoded by it to improve the reprogramming of differentiated cells to an embryonic-like state. Here I review the effects of vitamins A and C on DNA methylation and epigenetic memory in stem cells, and outline their significance for the fields For reprint orders, please contact: reprints@futuremedicine.com

show abstract

“…At the molecular level, the expression of genes within imprinted regions is influenced by specific patterns of DNA methylation, changes in chromatin structure, and post-translational histone modifications, collectively designated as epigenetic regulation (for review: [2,3]). So far, more than 90 human genes have been confirmed to be imprinted, but there are probably more based on bioinformatics predictions Their programming is subject to an imprinting cycle during life which leads to a reprogramming at each generation (for review: [4,5]). Methylation of the mammalian genome is comprehensively remodelled in early development.…”

Section: Introductionmentioning

confidence: 99%

Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management

Soellner

Monk

Rezwan

et al. 2015

Molecular and Cellular Probes

View full text Add to dashboard Cite

Imprinting disorders (IDs) are a group of congenital diseases affecting growth, development and metabolism. They are caused by changes in the allele-specific regulation ("epigenetic mutation") or in the genomic sequence ("genetic mutation") of imprinted genes. Currently molecular tests in ID patients are generally restricted to single loci classically associated with the disease, but this approach limits diagnostic yield, because of the molecular and clinical heterogeneity between IDs. From the technical point of view, these limitations are aggravated by the lack of standardization in testing methodology, in the DNA sequences tested, and in clinical inclusion criteria prompting testing.However, an increasing number of new studies show that these problems can be addressed by the use of new tests targeting multiple loci and/or a total exome and genome analysis.The rapid development of efficient and high-throughput molecular techniques and their applications in research and diagnostics in the last decade have led to an impressive increase of knowledge on IDs and their basic pathomechanisms. In combination with the improvement of data recording and documentation, the diagnostic strategies are increasingly based on standardized protocols, and thereby provide the backbone for directed counselling, more personalized management, and new therapeutic approaches.

show abstract

The role of genomic imprinting in biology and disease: an expanding view

Cited by 401 publications

References 159 publications

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

Effect of high fat diet on paternal sperm histone distribution and male offspring liver gene expression

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management

Contact Info

Product

Resources

About