Transgenerational epigenetic inheritance in plants

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Transgenerational epigenetic inheritance in plants involves mechanisms for the passing of epigenetic marks from parent to offspring that differ from those reported in animals. [1] 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.

Contents

In eukaryotes, negatively-charged DNA is wrapped extremely tightly around positively-charged proteins, called histones, to form chromatin. [2] Since the DNA is wrapped so tightly, it is inaccessible to transcription enzymes that function to copy the DNA into RNA (See: Central dogma of molecular biology). The inaccessible DNA must be unwound to be transcribed into RNA. The mechanism by which the DNA can be unwound is called chromatin remodeling. Chromatin remodeling is one apparatus through which epigenetics acts.

Mechanisms

There are three mechanisms of chromatin remodeling that are well-supported by research:

DNA methylation

DNA methylation refers to the addition of a methyl group (CH3) to a cytosine (C) nucleotide in DNA. [2] In plants, methylation occurs in every cytosine sequence context (CG, CHG and CHH where H represents either A, T, or C). [3] The addition of a methyl group to a C nucleotide manipulates DNA expression patterns by changing the availability of genes for transcription. DNA methylation has also been shown to prevent disruption in the DNA sequence by repressing transposable elements.

DNA methylation patterns in plants are more complex than in animals and these patterns must be maintained to ensure their successful transfer to progeny. [3] There are three pathways for maintenance of DNA methylation patterns in plants: the maintenance of CG by the enzyme MET1 (DNA Methyltransferase 1), the CMT3/SUVH pathway, and the RNA-dependent DNA methylation pathway (RdDM).

The first is the maintenance of CG by MET1. In plants, CG methylation is the most common context in which DNA methylation appears, and it is faced with the most scrutiny during maintenance. [3] After DNA replication, the previously methylated CG sites become hemi-methylated – the term given to the asymmetric status of a newly-synthesized strand of DNA in which the parent strand is methylated and the daughter strand is not. [3] [4] MET1 is recruited to the site of hemi-methylated CG and, with the help of enzymes, copies the methylation of the parent strand onto the daughter strand. [3]

The second pathway – called the CMT3/SUVH pathway – methylates CHG contexts using the enzyme CMT3 (Chromomethylase 3) in conjunction with the histone H3K9me which is maintained by enzymes called SUVH histone methyltransferases (Mtases). [3] [5] The SUVH enzymes contain a binding domain for methylated cytosines and CMT3 has a binding domain for H3K9me. [5] The existence of these binding domains suggests that among DNA methylation and H3K9me, a self-reinforcing loop – a metabolic cycle – maintains the repression of transposable elements and repeats. [3] [5]

The third pathway for maintenance of DNA methylation patterns in plants is a pathway called RNA-dependent DNA Methylation (RdDM). [3] The enzyme CMT2 maintains cytosine methylation in CHH sequence contexts. The methylation of CHH is asymmetric, meaning that the normal degradation of methylation that occurs during DNA replication will be maintained and the methylation will be lost in one daughter strand.

Although these three pathways are distinct, there is cross-talk among them. [3] Some non-CG contexts require MET1 and some CHH contexts require the CMT3/SUVH pathway.

Demethylation is the removal of methyl groups from DNA. Plants are unique in their use of active DNA demethylation. [6] They use the Base Excision Repair (BER) pathway to remove methylated cytosines and replace them with unmodified ones. Glycosylases catalyze the removal of the single methylated cytosines and DNA repair enzymes clean the ends and add new cytosines.

Histone modification

Histone modification refers to the addition or subtraction of certain chemical groups from the amino acids of histones that change transcription activity by initiating a change in the structure of the chromatin or by recruiting transcription enzymes. [2] [7] Mediation of chromatin occurs most frequently through post-translational modifications like methylation, acetylation, ubiquitination, and phosphorylation, which are the main histone modifications occurring in plants. [7] [8]   Usually, the addition of a histone modification increases transcription by neutralizing the positive charge of the histones and, thereby, unwinding the negatively-charged DNA. [9] Histone writers, readers, and erasers are the regulatory machinery that recognize and modify the histone modifications. [8] Writers add, erasers remove, and readers recognize the post-translational modifications of histones. Each writer, reader and eraser is further subdivided based on the type of post-translational modification they act on or recognize.

Chromatin-remodeling complexes

Chromatin-remodeling complexes are protein complexes that change the composition of and interactions among nucleosomes, thus changing chromatin structure and DNA expression patterns. [10] These ATP-dependent protein complexes are divided into four subfamilies: the SWI/SNF Subfamily, the Imitation Switch (ISWI) Subfamily, the Chromodomain Helicase DNA-Binding (CHD) Subfamily, and the Inositol Requiring 80 (INO80) Subfamily. SWI/SNF chromatin remodelers work to promote transcription by ejecting nucleosomes at specific positions on the chromosome but they are thought to have a minimal role in eukaryotic chromatin structure. ISWI Subfamily remodelers inhibit transcription by regulating the spacing of nucleosomes. CDH Subfamily remodelers are very diverse and vary in their structure and function. Some CDH subfamily remodelers repress transcription while others promote it. Lastly, INO80 Subfamily remodelers are highly conserved meaning that they have similar structures and functions across many species. Not only do they function to promote transcription, INO80s also play a role in DNA double-strand break repair.

Evolutionary perspective

Plants are immobile, so they are under especially strong pressure to adapt quickly and effectively to their environment. [1] Seed dormancy and germination is an example of a plant function that is heavily mediated by epigenetics – by histone modification. [7] When histones are deacetylated, the transcription of photosynthesis genes is ‘turned off’ and germination is arrested. Stressful events like drought, exposure to UV radiation, cold, and pathogens have been seen to trigger a heritable increase in the frequency of recombination. [11] [12] [13] [14] [1] The increase in recombination frequency allows for an increase in genetic variation. The more variation within a population, the greater the possibility that a well-adapted genotype will arise for selection to act on during stress-inducing environmental conditions. [1]

DNA methylation is a refined regulator of gene expression; controlling which genes to express and how much to express them. [15] Consequently, phenotypes induced by methylation are continuous, rather than being discrete. For example, crosses of wildtype and methylated mutant Linaria vulgaris plants resulted in offspring that varied in their methylation of the gene controlling floral symmetry: Lcyc. [16] By proxy, their expression of Lcyc was varied and their floral symmetry phenotypes were a continuous distribution ranging from radially symmetrical to bilaterally symmetrical and anywhere in between. Cubas et al.’s (1999) experiment characterized the first natural morphological mutant. This mutation of the Lcyc gene in Linaria vulgaris causes the flower to become radially symmetrical as opposed to bilaterally symmetrical. The authors found that, in the mutant, Lcyc is highly methylated which prohibits the transcription of the gene; effectively silencing it. Consequently, in wildtypes, growth of the dorsal stamen (the male organ of the flower) is arrested early-on in its development but, in mutants, the development of the dorsal stamen persists. Additionally, the dorsal petal develops similarly to neighboring petals in mutants, but in wildtypes, the dorsal petal is unique. The naturally-occurring methylation of Lcyc was found to be heritable and reversible.

An influential experiment by Jacobsen and Meyerowitz (1997) characterized seven epigenetic alleles (epialleles) of the SUPERMAN (SUP) gene in Arabidopsis thaliana. [17] These seven epialleles are referred to as the clark kent alleles (clk 1-7) and they are associated with hypermethylation in SUP. The SUP gene controls flower development in Arabidopsis and the presence of a clk allele is correlated with an increase in the number of stamens and carpels (the female organ of the flower) in the first ten flowers of each plant. Additionally, the presence of clk alleles is associated with a reduction in SUP RNA expression which, in wild type plants, occurs within developing stamens during the establishment of floral meristems.

These examples of epigenetics in nature demonstrate the ability of epialleles to drastically influence phenotypes and increase genetic variability within populations. The stable heritability of epigenetic marks across generations suggests that resulting phenotypes would have substantial fitness effects and may respond, as DNA sequence variation does, to natural selection. [15] The changes that epialleles induce can be quickly turned on and just as quickly degraded resulting in phenotypic plasticity. The heritability of epigenetic marks can serve as a generational memory to better prepare progeny for local environmental conditions.

Related Research Articles

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

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.

<span class="mw-page-title-main">Euchromatin</span> Lightly packed form of chromatin that is enriched in genes

Euchromatin is a lightly packed form of chromatin that is enriched in genes, and is often under active transcription. Euchromatin stands in contrast to heterochromatin, which is tightly packed and less accessible for transcription. 92% of the human genome is euchromatic.

In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and the biological sciences.

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.

<span class="mw-page-title-main">DNA methyltransferase</span> Class of enzymes

In biochemistry, the DNA methyltransferase family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor.

<span class="mw-page-title-main">Histone methyltransferase</span> Histone-modifying enzymes

Histone methyltransferases (HMT) are histone-modifying enzymes, that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of histone proteins. The attachment of methyl groups occurs predominantly at specific lysine or arginine residues on histones H3 and H4. Two major types of histone methyltranferases exist, lysine-specific and arginine-specific. In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.
The genomic DNA of eukaryotes associates with histones to form chromatin. The level of chromatin compaction depends heavily on histone methylation and other post-translational modifications of histones. Histone methylation is a principal epigenetic modification of chromatin that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis.

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

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.

<span class="mw-page-title-main">DNA methylation</span> Biological process

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.

<span class="mw-page-title-main">Paramutation</span>

In epigenetics, a paramutation is an interaction between two alleles at a single locus, whereby one allele induces a heritable change in the other allele. The change may be in the pattern of DNA methylation or histone modifications. The allele inducing the change is said to be paramutagenic, while the allele that has been epigenetically altered is termed paramutable. A paramutable allele may have altered levels of gene expression, which may continue in offspring which inherit that allele, even though the paramutagenic allele may no longer be present. Through proper breeding, paramutation can result in siblings that have the same genetic sequence, but with drastically different phenotypes.

<span class="mw-page-title-main">Methyltransferase</span> Group of methylating enzymes

Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). Class II methyltransferases contain a SET domain, which are exemplified by SET domain histone methyltransferases, and class III methyltransferases, which are membrane associated. Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. SAM is the classical methyl donor for methyltransferases, however, examples of other methyl donors are seen in nature. The general mechanism for methyl transfer is a SN2-like nucleophilic attack where the methionine sulfur serves as the leaving group and the methyl group attached to it acts as the electrophile that transfers the methyl group to the enzyme substrate. SAM is converted to S-Adenosyl homocysteine (SAH) during this process. The breaking of the SAM-methyl bond and the formation of the substrate-methyl bond happen nearly simultaneously. These enzymatic reactions are found in many pathways and are implicated in genetic diseases, cancer, and metabolic diseases. Another type of methyl transfer is the radical S-Adenosyl methionine (SAM) which is the methylation of unactivated carbon atoms in primary metabolites, proteins, lipids, and RNA.

Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.

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.

Embryonic stem cells are capable of self-renewing and differentiating to the desired fate depending on their position in the body. Stem cell homeostasis is maintained through epigenetic mechanisms that are highly dynamic in regulating the chromatin structure as well as specific gene transcription programs. Epigenetics has been used to refer to changes in gene expression, which are heritable through modifications not affecting the DNA sequence.

RNA polymerase V, previously known as RNA polymerase IVb, is a multisubunit plant specific RNA polymerase. It is required for normal function and biogenesis of small interfering RNA (siRNA). Together with RNA polymerase IV, Pol V is involved in an siRNA-dependent epigenetic pathway known as RNA-directed DNA methylation (RdDM), which establishes and maintains heterochromatic silencing in plants.

<span class="mw-page-title-main">Epigenetics of human herpesvirus latency</span>

Human herpes viruses, also known as HHVs, are part of a family of DNA viruses that cause several diseases in humans. One of the most notable functions of this virus family is their ability to enter a latent phase and lay dormant within animals for extended periods of time. The mechanism that controls this is very complex because expression of viral proteins during latency is decreased a great deal, meaning that the virus must have transcription of its genes repressed. There are many factors and mechanisms that control this process and epigenetics is one way this is accomplished. Epigenetics refers to persistent changes in expression patterns that are not caused by changes to the DNA sequence. This happens through mechanisms such as methylation and acetylation of histones, DNA methylation, and non-coding RNAs (ncRNA). Altering the acetylation of histones creates changes in expression by changing the binding affinity of histones to DNA, making it harder or easier for transcription machinery to access the DNA. Methyl and acetyl groups can also act as binding sites for transcription factors and enzymes that further modify histones or alter the DNA itself.

Plants depend on epigenetic processes for proper function. Epigenetics is defined as "the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence". The area of study examines protein interactions with DNA and its associated components, including histones and various other modifications such as methylation, which alter the rate or target of transcription. Epi-alleles and epi-mutants, much like their genetic counterparts, describe changes in phenotypes due to epigenetic mechanisms. Epigenetics in plants has attracted scientific enthusiasm because of its importance in agriculture.

Pharmacoepigenetics is an emerging field that studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.

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.

<span class="mw-page-title-main">RNA-directed DNA methylation</span> RNA-based gene silencing process

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.

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