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An allele, or allelomorph, is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.
In biology, epigenetics are stable heritable traits that cannot be explained by changes in DNA sequence, and the study of a type of stable change in cell function that does not involve a change to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA, while at least 80% of mammalian genomic DNA can be actively transcribed, with the majority of this 80% considered to be ncRNA.
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands.
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.
Superman is a plant gene in Arabidopsis thaliana, that plays a role in controlling the boundary between stamen and carpel development in a flower. It is named for the comic book character Superman, and the related genes kryptonite (gene) and clark kent were named accordingly. It encodes a transcription factor. Homologous genes are known in the petunia and snapdragon, which are also involved in flower development, although in both cases there are important differences from the functioning in Arabidopsis. Superman is expressed early on in flower development, in the stamen whorl adjacent to the carpel whorl. It interacts with the other genes of the ABC model of flower development in a variety of ways.
Bisulfitesequencing (also known as bisulphite sequencing) is the use of bisulfite treatment of DNA before routine sequencing to determine the pattern of methylation. DNA methylation was the first discovered epigenetic mark, and remains the most studied. In animals it predominantly involves the addition of a methyl group to the carbon-5 position of cytosine residues of the dinucleotide CpG, and is implicated in repression of transcriptional activity.
Tiling arrays are a subtype of microarray chips. Like traditional microarrays, they function by hybridizing labeled DNA or RNA target molecules to probes fixed onto a solid surface.
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.
In genetics, DNase I hypersensitive sites (DHSs) are regions of chromatin that are sensitive to cleavage by the DNase I enzyme. In these specific regions of the genome, chromatin has lost its condensed structure, exposing the DNA and making it accessible. This raises the availability of DNA to degradation by enzymes, such as DNase I. These accessible chromatin zones are functionally related to transcriptional activity, since this remodeled state is necessary for the binding of proteins such as transcription factors.
ATAC-seq is a technique used in molecular biology to assess genome-wide chromatin accessibility. In 2013, the technique was first described as an alternative advanced method for MNase-seq, FAIRE-Seq and DNase-Seq. ATAC-seq is a faster analysis of the epigenome than DNase-seq or MNase-seq.
Whole genome bisulfite sequencing is a next-generation sequencing technology used to determine the DNA methylation status of single cytosines by treating the DNA with sodium bisulfite before high-throughput DNA sequencing. The DNA methylation status at various genes can reveal information regarding gene regulation and transcriptional activities. This technique was developed in 2009 along with reduced representation bisulfite sequencing after bisulfite sequencing became the gold standard for DNA methylation analysis.
An epigenome-wide association study (EWAS) is an examination of a genome-wide set of quantifiable epigenetic marks, such as DNA methylation, in different individuals to derive associations between epigenetic variation and a particular identifiable phenotype/trait. When patterns change such as DNA methylation at specific loci, discriminating the phenotypically affected cases from control individuals, this is considered an indication that epigenetic perturbation has taken place that is associated, causally or consequentially, with the phenotype.
Human epigenome is the complete set of structural modifications of chromatin and chemical modifications of histones and nucleotides. These modifications affect according to cellular type and development status. Various studies show that epigenome depends on exogenous factors.
RNA-directed DNA methylation (RdDM) is a biological process in which non-coding RNA molecules direct the addition of DNA methylation to specific DNA sequences. The RdDM pathway is unique to plants, although other mechanisms of RNA-directed chromatin modification have also been described in fungi and animals. To date, the RdDM pathway is best characterized within angiosperms, and particularly within the model plant Arabidopsis thaliana. However, conserved RdDM pathway components and associated small RNAs (sRNAs) have also been found in other groups of plants, such as gymnosperms and ferns. The RdDM pathway closely resembles other sRNA pathways, particularly the highly conserved RNAi pathway found in fungi, plants, and animals. Both the RdDM and RNAi pathways produce sRNAs and involve conserved Argonaute, Dicer and RNA-dependent RNA polymerase proteins.
Transgenerational epigenetic inheritance in plants involves mechanisms for the passing of epigenetic marks from parent to offspring that differ from those reported in animals. There are several kinds of epigenetic markers, but they all provide a mechanism to facilitate greater phenotypic plasticity by influencing the expression of genes without altering the DNA code. These modifications represent responses to environmental input and are reversible changes to gene expression patterns that can be passed down through generations. In plants, transgenerational epigenetic inheritance could potentially represent an evolutionary adaptation for sessile organisms to quickly adapt to their changing environment.
Nucleosome Occupancy and Methylome Sequencing (NOMe-seq) is a genomics technique used to simultaneously detect nucleosome positioning and DNA methylation... This method is an extension of bisulfite sequencing, which is the gold standard for determining DNA methylation. NOMe-seq relies on the methyltransferase M.CviPl, which methylates cytosines in GpC dinucleotides unbound by nucleosomes or other proteins, creating a nucleosome footprint. The mammalian genome naturally contains DNA methylation, but only at CpG sites, so GpC methylation can be differentiated from genomic methylation after bisulfite sequencing. This allows simultaneous analysis of the nucleosome footprint and endogenous methylation on the same DNA molecules. In addition to nucleosome foot-printing, NOMe-seq can determine locations bound by transcription factors. Nucleosomes are bound by 147 base pairs of DNA whereas transcription factors or other proteins will only bind a region of approximately 10-80 base pairs. Following treatment with M.CviPl, nucleosome and transcription factor sites can be differentiated based on the size of the unmethylated GpC region.
References
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- ↑ Schmitz, Robert J.; Schultz, Matthew D.; Urich, Mark A.; Nery, Joseph R.; Pelizzola, Mattia; Libiger, Ondrej; Alix, Andrew; McCosh, Richard B.; Chen, Huaming; Schork, Nicholas J.; Ecker, Joseph R. (2013). "Patterns of population epigenomic diversity". Nature. 495 (7440): 193–198. Bibcode:2013Natur.495..193S. doi:10.1038/nature11968. PMC 3798000 . PMID 23467092.
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- ↑ Bewick, Adam J.; Ji, Lexiang; Niederhuth, Chad E.; Willing, Eva-Maria; Hofmeister, Brigitte T.; Shi, Xiuling; Wang, Li; Lu, Zefu; Rohr, Nicholas A.; Hartwig, Benjamin; Kiefer, Christiane; Deal, Roger B.; Schmutz, Jeremy; Grimwood, Jane; Stroud, Hume; Jacobsen, Steven E.; Schneeberger, Korbinian; Zhang, Xiaoyu; Schmitz, Robert J. (2016). "On the origin and evolutionary consequences of gene body DNA methylation". Proceedings of the National Academy of Sciences. 113 (32): 9111–9116. Bibcode:2016PNAS..113.9111B. doi: 10.1073/pnas.1604666113 . PMC 4987809 . PMID 27457936.
- ↑ Hofmeister, Brigitte T.; Lee, Kevin; Rohr, Nicholas A.; Hall, David W.; Schmitz, Robert J. (2017). "Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation". Genome Biology. 18 (1): 155. doi: 10.1186/s13059-017-1288-x . PMC 5559844 . PMID 28814343.
- ↑ "UGA researchers develop method to improve crops". 6 March 2018.
- ↑ Ji, Lexiang; Jordan, William T.; Shi, Xiuling; Hu, Lulu; He, Chuan; Schmitz, Robert J. (2018). "TET-mediated epimutagenesis of the Arabidopsis thaliana methylome". Nature Communications. 9 (1): 895. Bibcode:2018NatCo...9..895J. doi:10.1038/s41467-018-03289-7. PMC 5832761 . PMID 29497035.
- ↑ Ricci, William A.; Lu, Zefu; Ji, Lexiang; Marand, Alexandre P.; Ethridge, Christina L.; Murphy, Nathalie G.; Noshay, Jaclyn M.; Galli, Mary; Mejía-Guerra, María Katherine; Colomé-Tatché, Maria; Johannes, Frank; Rowley, M. Jordan; Corces, Victor G.; Zhai, Jixian; Scanlon, Michael J.; Buckler, Edward S.; Gallavotti, Andrea; Springer, Nathan M.; Schmitz, Robert J.; Zhang, Xiaoyu (2019). "Widespread long-range cis-regulatory elements in the maize genome". Nature Plants. 5 (12): 1237–1249. doi:10.1038/s41477-019-0547-0. PMC 6904520 . PMID 31740773.
- ↑ Lu, Zefu; Hofmeister, Brigitte T.; Vollmers, Christopher; Dubois, Rebecca M.; Schmitz, Robert J. (2017). "Combining ATAC-seq with nuclei sorting for discovery of cis-regulatory regions in plant genomes". Nucleic Acids Research. 45 (6): e41. doi:10.1093/nar/gkw1179. PMC 5389718 . PMID 27903897.
- ↑ "Schmitz, Robert J. - Institute for Advanced Study (IAS)".
