DNA methylation and epigenetic inheritance

Classical genetics has revealed the mechanisms for the transmission of genes from generation to generation, but the strategy of the genes in unfolding the developmental programme remains obscure. Epigenetics comprises the study of the mechanisms that impart temporal and spatial control on the activities of all those genes required for the development of a complex organism from the zygote to the adult. Epigenetic changes in gene activity can be studied in relation to DNA methylation in cultured mammalian cells and it is also possible to isolate and characterize mutants with altered DNA methylase activity. Although this experimental system is quite far removed from the epigenetic controls acting during development it does provide the means to clarify the rules governing the silencing of genes by specific DNA methylation and their reactivation by demethylation. This in turn will facilitate studies on the control of gene expression in somatic cells of the developing organism or the adult. The general principles of epigenetic mechanisms can be defined. There are extreme contrasts between instability or switches in gene expression, such as those in stem-line cells, and the stable heritability of a specialized pattern of gene activities. In some situations cell lineages are known to be important, whereas in others coordinated changes in groups of cells have been demonstrated. Control of numbers of cell divisions and the size of organisms, or parts of organisms, is also essential. The epigenetic determination of gene expression can be reversed or reprogrammed in the germ line. The extent to which methylation or demethylation of specific DNA sequences can help explain these basic epigenetic mechanisms is briefly reviewed.

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DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38

Epigenetics Insights ◽

10.1177/2516865718811117 ◽

2018 ◽

Vol 11 ◽

pp. 251686571881111 ◽

Cited By ~ 5

Author(s):

Maud de Dieuleveult ◽

Benoit Miotto

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Transcription Factors ◽

Dna Sequences ◽

Mammalian Cells ◽

Expression Patterns ◽

Control Of Gene Expression ◽

Methylated Dna

DNA methylation plays an essential role in the control of gene expression during early stages of development as well as in disease. Although many transcription factors are sensitive to this modification of the DNA, we still do not clearly understand how it contributes to the establishment of proper gene expression patterns. We discuss here the recent findings regarding the biological and molecular function(s) of the transcription factor ZBTB38 that binds methylated DNA sequences in vitro and in cells. We speculate how these findings may help understand the role of DNA methylation and DNA methylation–sensitive transcription factors in mammalian cells.

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Epigenetic inheritance and genome regulation: is DNA methylation linked to ploidy in haplodiploid insects?

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.0411 ◽

2014 ◽

Vol 281 (1785) ◽

pp. 20140411 ◽

Cited By ~ 21

Author(s):

Karl M. Glastad ◽

Brendan G. Hunt ◽

Soojin V. Yi ◽

Michael A. D. Goodisman

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Solenopsis Invicta ◽

Copy Number ◽

Epigenetic Inheritance ◽

Epigenetic Mechanisms ◽

Diploid Males ◽

Epigenetic Information ◽

Haploid Male ◽

Genome Copy Number

Organisms show great variation in ploidy level. For example, chromosome copy number varies among cells, individuals and species. One particularly widespread example of ploidy variation is found in haplodiploid taxa, wherein males are typically haploid and females are typically diploid. Despite the prevalence of haplodiploidy, the regulatory consequences of having separate haploid and diploid genomes are poorly understood. In particular, it remains unknown whether epigenetic mechanisms contribute to regulatory compensation for genome dosage. To gain greater insights into the importance of epigenetic information to ploidy compensation, we examined DNA methylation differences among diploid queen, diploid worker, haploid male and diploid male Solenopsis invicta fire ants. Surprisingly, we found that morphologically dissimilar diploid males, queens and workers were more similar to one another in terms of DNA methylation than were morphologically similar haploid and diploid males. Moreover, methylation level was positively associated with gene expression for genes that were differentially methylated in haploid and diploid castes. These data demonstrate that intragenic DNA methylation levels differ among individuals of distinct ploidy and are positively associated with levels of gene expression. Thus, these results suggest that epigenetic information may be linked to ploidy compensation in haplodiploid insects. Overall, this study suggests that epigenetic mechanisms may be important to maintaining appropriate patterns of gene regulation in biological systems that differ in genome copy number.

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Decoding the Chromatin Code

Blood ◽

10.1182/blood.v120.21.sci-4.sci-4 ◽

2012 ◽

Vol 120 (21) ◽

pp. SCI-4-SCI-4

Author(s):

Peter A. Jones

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Transcription Start Site ◽

Cpg Islands ◽

Epigenetic Inheritance ◽

Promoter Hypermethylation ◽

Start Site ◽

Transcription Start ◽

Control Of Gene Expression ◽

Transcriptional Start Sites

Abstract Abstract SCI-4 Epigenetic processes are reinforced by interactions between covalent chromatin marks such as DNA methylation, histone modifications, and variants thereof. These marks ultimately specify the locations of nucleosomes, particularly with respect to transcriptional start sites and other regulatory regions. Understanding how the epigenome functions, therefore, requires a coordinated approach in order to reveal the mechanisms by which the chemical modifications interact with nucleosomal remodeling machines to ensure epigenetic inheritance and control of gene expression. We have developed a new methodology to simultaneously map nucleosomal positioning and DNA methylation on individual molecules of DNA. We used this nucleosomal mapping technology to ascertain alterations in nucleosomal positioning during the abnormal silencing of genes by promoter hypermethylation. These experiments show that the methylation of CpG islands at the transcriptional start sites of key tumor-suppressor genes results in the stable placement of nucleosomes at the transcription start site. Treatment with 5-azanucleoside results in an immediate inhibition of DNA methylation and a sequence of downstream events that ultimately result in the eviction of the nucleosomes from the transcription start site and the activation of gene expression. Disclosures: Jones: Eli Lilly: Consultancy.

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High-performance chemical- and light-inducible recombinases in mammalian cells and mice

Nature Communications ◽

10.1038/s41467-019-12800-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Benjamin H. Weinberg ◽

Jang Hwan Cho ◽

Yash Agarwal ◽

N. T. Hang Pham ◽

Leidy D. Caraballo ◽

...

Keyword(s):

Gene Expression ◽

Mammalian Cells ◽

High Performance ◽

Genome Engineering ◽

Genetic Circuits ◽

Control Of Gene Expression ◽

Expression Control ◽

Gene Expression Control ◽

High Performance Systems ◽

Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

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Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction

RNA ◽

10.1261/rna.2299306 ◽

2006 ◽

Vol 12 (5) ◽

pp. 710-716 ◽

Cited By ~ 107

Author(s):

C.-I. An

Keyword(s):

Gene Expression ◽

Rna Interference ◽

Small Molecule ◽

Mammalian Cells ◽

Control Of Gene Expression ◽

Expression In Mammalian Cells ◽

Molecule Interaction ◽

Artificial Control

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Nurse cell-derived small RNAs define paternal epigenetic inheritance in Arabidopsis

10.1101/2021.01.25.428150 ◽

2021 ◽

Author(s):

Jincheng Long ◽

James Walker ◽

Wenjing She ◽

Billy Aldridge ◽

Hongbo Gao ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Small Rnas ◽

Nurse Cell ◽

De Novo ◽

Epigenetic Inheritance ◽

Genome Integrity ◽

Nurse Cells ◽

Male Germline ◽

Methylation Patterns

AbstractThe plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and facilitates meiosis. Why reprogramming is limited to the germline and how specific genes are chosen is unknown. Here, we demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by germline-specific siRNAs transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) via activity of the tapetum-specific chromatin remodeler CLASSY3. Remarkably, tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Finally, we demonstrate that these nurse cell-derived siRNAs (niRNAs) silence germline transposons, thereby safeguarding genome integrity. Our results reveal that tapetal niRNAs are sufficient to reconstitute germline methylation patterns and drive extensive, functional methylation reprogramming analogous to piRNA-mediated reprogramming in animal germlines.

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Intergenerational epigenetic inheritance in reef-building corals

10.1101/269076 ◽

2018 ◽

Cited By ~ 6

Author(s):

Yi Jin Liew ◽

Emily J. Howells ◽

Xin Wang ◽

Craig T. Michell ◽

John A. Burt ◽

...

Keyword(s):

Dna Methylation ◽

Intergenerational Transmission ◽

Epigenetic Inheritance ◽

Cpg Methylation ◽

Epigenetic Mechanisms ◽

Transgenerational Inheritance ◽

Genome Wide ◽

Methylation Patterns ◽

Hypermethylated Genes

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.

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Epigenetics

Oxford Textbook of Cancer Biology ◽

10.1093/med/9780198779452.003.0005 ◽

2019 ◽

pp. 56-70

Author(s):

Edward Hookway ◽

Nicholas Athanasou ◽

Udo Oppermann

Keyword(s):

Gene Expression ◽

Histone Deacetylases ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Tumour Suppressor Genes ◽

Epigenetic Mechanisms ◽

Therapeutic Approaches ◽

Control Of Gene Expression ◽

Non Coding Rnas ◽

Epigenetic Processes

Epigenetics is a term that refers to a collection of diverse mechanisms that are important in both the control of gene expression and the transmission of this information during cell division. Epigenetic processes are deranged in many cancers, leading to a combination of inappropriate silencing of tumour suppressor genes and overexpression of oncogenes. In this chapter, the molecular mechanisms that underpin the major epigenetic processes of DNA methylation, histone modification, and non-coding RNAs will be described in both their normal physiological roles and in the context of cancer. The challenge of understanding the complexity of the interactions between different epigenetic mechanisms and the limitations of our current knowledge will be highlighted. Therapeutic approaches towards targeting deranged epigenetic processes will also be described, such as the use of small molecule inhibitors of histone deacetylases.

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