Epigenetics Book

The Most Comprehensive Exploration of the Practical, Social and Ethical Impact of DNA on Our Society and Our World

Roy Carroll

• Publisher: Youcanprint
• Year: 2022
• ISBN:
  9791220372398
• Topic: Medicine
• Subtopic: Genetics in Medicine

You Are About To Develop An Insider Understanding Of Epigenetics, Including Their Relationship With The DNA, Environmental Factors, Human Development And Evolution; Their Role In Human Mental And Physical Health, Including Their Use In The Treating Of Different Conditions And Diseases Along With The Most Current Epigenetic Practices And Research! What started as a broad research focused on combining genetics and developmental biology during the mid-twentieth century has evolved into the field we currently refer to as epigenetics- the mechanism of gene control that can either promote or repress gene expression without altering the genetic coding of the organism. Today, we know that the environment factors and individual lifestyles can have a direct interaction with epigenetic change, which can be reflected at various stages throughout the life of an individual and even in the later generations. You've heard that a mother's exposure to pollution can affect her child's asthma susceptibility, haven't you? No? How about the argument that a child's mental fitness can be (epigenetically) influenced by his/her dad's diet? Epigenetic change, which has nothing to do with the changes to the underlying DNA sequence, does affect how cells read genes and this biological change is influenced by several factors which include environment, lifestyle and health state through a mechanisms including a popular one known as DNA methylation. But what is the relationship between the epigenetic change and physical and physiological conditions as regards to their onset and improvement? How are epigenetic modifications being used to understand our environment, society and increasing human adaptation? How exactly do epigenetic therapies work? How does DNA affect epigenetic changes? How can we exploit epigenetic mechanisms to understand life better and improve it? If you have these and other related questions, this book is for you. More precisely, you will learn: What epigenetics are and their role in developmental psychology The influence of epigenetics at the molecular level and the impact of DNA damage in epigenetic change How epigenetics are studied The functions and consequences of epigenetics, and their specific benefits in mindfulness training, healthy eating and physical activity How genes control the growth and division of cells The role of epigenetic therapy in diabetic retinopathy, emotional disorders, cardiac dysfunction, cancer and schizophrenia and many more How epigenetic modifications are used in cancer treatment, and plant and animal evolution How epigenetic mechanisms are used in processes including human adaptation, memory formation, growth and infant neuro-behavior. How epigenetic mechanisms are used in maternal care How environmental chemical exposures affect epigenetics The role of epigenetics in neurodegenerative diseases, drug formation, human development, the development of Hox genes and many more The role of environmental exposures in pathophysiology of IPF Modulation of epigenetic marks by environmental exposures How epigenetic regulation affects the immune system …And so much more! So if you've been exposed to the concept of epigenetics as a novel way of understanding disorders, inheritance and evolution and wondered what it's really all about and how it's related with environmental exposure and different therapy practices, this book is all you need! Scroll up and click Buy Now With 1-Click or Buy Now to get started!

Chapter One

About Epigenetics

In biology, epigenetics is the study

of heritable phenotype changes that do not involve alterations in the DNA sequence. The Greek prefix epi- over, outside of, around") in epigenetics implies features that are "on top of" or

"in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable in the progeny of either cells or organisms.

The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations, even though they do not

involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.

One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation.

During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell – the zygote – continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neurons, muscle

cells, epithelium, endothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.

Historically, some phenomena not necessarily heritable have also been described as epigenetic. For example, the term

"epigenetic" has been used to describe any modification of chromosomal regions, especially histone modifications, whether or not these changes are heritable or associated with a phenotype. The consensus definition now requires a trait to be heritable for it to be considered epigenetic.

The term epigenetics in its contemporary usage emerged in the 1990s, but for some years has been used with somewhat variable meanings. A consensus definition of the concept of epigenetic trait as a "stably heritable phenotype resulting from changes in a

chromosome without alterations in the DNA sequence" was formulated at a Cold Spring Harbor meeting in 2008, although alternate definitions that include non-heritable traits are still being used.

The term epigenesis has a generic meaning of "extra growth", and has been used in English since the 17th century.

Developmental psychology

In a somewhat different context to its usage in biological sciences, the word "epigenetic" has often been used in developmental psychology to define psychological growth as a product of a constant, bi-directional interaction between heredity and the environment. Interactive theories about creation have been explored in numerous ways and under multiple titles in the 19th and 20th centuries. An early edition, among the founding statements of embryology, was suggested by Karl Ernst von Baer and popularized by Ernst Haeckel. Paul Wintrebert has developed a progressive epigenetic dream (physiological epigenesis). Another form, probabilistic epigenesis, was described in 2003 by Gilbert Gottlieb. This perspective covers all potential evolutionary effects on the organism and how they affect not just the organism and each other, but also how the organism affects its own growth.

Erik Erik Erikson, a developmental psychologist, wrote about the epigenetic concept in his 1968 book Identity: Youth and Crisis, which incorporates the idea that we grow through the evolution of our personalities in fixed phases, and that our atmosphere and underlying society affect how we advance through these phases. This biological evolution in relation to our socio-cultural environments takes place at the level of psychosocial progression, where "progress in each level is partially decided by our performance or lack of success in all previous stages." While empiric experiments have produced varying findings, epigenetic changes are believed to be a biological trigger for transgenerational trauma.

Molecular basis

Epigenetic shifts affect the function of other genes, but not the DNA gene code chain. The microstructure (not the code) of DNA itself or the related chromatin proteins can be changed, resulting in activation or silencing. This process enables segregated cells in a multicellular organism to produce only the genes required for their own activity. Epigenetic variations are retained as the cells separate. Some epigenetic modifications arise only over the lifespan of an adult organism; nevertheless, these epigenetic changes may be passed to the descendants of the organism by a mechanism called transgenerational epigenetic inheritance. In fact, if gene inactivation happens in a

sperm or egg cell that results in fertilization, this epigenetic alteration can often be passed to the next generation.

Different epigenetic mechanisms include paramuting, bookmarking, imprinting, gene silencing, X-chromosome inactivation, positioning influence, reprogramming of DNA methylation, transvection, maternal results, advancement in carcinogenesis, a broad variety of teratogenic effects, histone and heterochromatin control, and technological constraints concerning parthenogenesis and cloning.

DNA damage

DNA damage may also induce epigenetic changes.[25][26][27]

DNA damage is very normal, occurring on average around 60,000 times a day per human body cell (see DNA damage (naturally occurring). These damages are mostly remedied, but epigenetic modifications can remain at the DNA repair site. In particular, a double-stranded DNA split will cause unprogrammed epigenetic gene silencing both by inducing DNA methylation and by facilitating the silencing of histone alteration forms (Chromatin remodeling-see next section). In addition, the enzyme Parp1 (poly(ADP)-ribose polymerase) and its component poly(ADP)-ribose (PAR) accumulate at DNA damage sites as part of the repair phase. Such aggregation, in effect, drives recruitment and activation of the ALC1 chromatin remodeling protein that may induce nucleosome remodeling.

Nucleosome remodeling has been shown to induce, for example,

epigenetic silencing of the MLH1 DNA repair gene. DNA harmful chemicals, such as benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene, cause considerable hypomethylation of DNA, some through the triggering of oxidative stress pathways.

Foods are known to change the epigenetics of rats in various diets. Some food components epigenetically raise the amount of DNA repair enzymes, such as MGMT and MLH1 and p53. Other food components, such as soy isoflavones, may reduce DNA damage. In one test, oxidative stress indicators, such as changed nucleotides that may result from DNA injury, were reduced by a 3-week diet complemented with soy. Decreased oxidative DNA damage was also detected 2 h after anthocyanin-rich bilberry (Vaccinium myrtillius L.) extract of pomace was eaten.

Techniques used to study epigenetics

Epigenetic work utilizes a broad variety of molecular biological methods to better explain epigenetic processes, including chromatin immunoprecipitation (together with its large-scale versions ChIP-on-chip and ChIP-Seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase recognition (DamID) and bisulphite sequencing. In fact, the application of bioinformatics has a role to play in statistical epigenetics.

Mechanisms Some forms of epigenetic inheritance mechanisms may have a function to play in what has become recognized as cell memory, but note that not all of them are widely acknowledged as examples of epigenetics.

Covalent changes Covalent variations in either DNA (e.g.

cytosine methylation and hydroxymethylation) or histone proteins (e.g. lysine acetylation, lysine and arginine methylation, serine and threonine phosphorylation, and lysine ubiquitination and sumoylation) play a key role in certain forms in epigenetic inheritance. The term "epigenetics" is often used as a synonym for such processes. Nevertheless, that could be deceptive. The remodeling of chromatin is not necessarily hereditary, so not all epigenetic inheritance includes the remodeling of chromatin. In 2019, a further alteration of lysine emerged in the scientific literature relating epigenetic change to cell metabolism, i.e.

Lactylation DNA is paired with histone proteins to form chromatin.

Since a cell or person phenotype is influenced by which of its genes are transcribed, inherited transcription states can give rise to epigenetic effects. There are many levels of gene expression control. One way genes are controlled is by chromatin remodeling. Chromatin is a complex of DNA and histone proteins in which it is linked. If the way the DNA is wound around the histones shifts, gene expression will also alter. The remodeling of chromatin is done by two primary mechanisms:

the first is the post-translational alteration of the amino acids that make up histone proteins. Histone proteins are made up of a long sequence of amino acids. When the amino acids in the chain are altered, the structure of the histone may be affected.

During replication, DNA is not fully unwound. It is also likely that the changed histones can be added to each fresh copy of the DNA. From there, these histones will serve as models, triggering new histones around them to be formed in a different way. By changing the structure of the histones surrounding them, these changed histones will guarantee that the lineage-specific transcription system is retained during the separation of the cells.

The second approach is to attach methyl groups to the DNA, often at CpG levels, to transform cytosine to 5-methylcytosine.

5-Methylcytosine has a comparable influence to normal cytosine, combined with guanine in double-stranded DNA.

However, certain parts of the genome are more methylated than others, and heavily methylated regions appear to be less transcriptionally involved by a process that is not well understood. Cytosine methylation may often continue from the germ line of one parent to the zygote, suggesting that the chromosome is transmitted by one parent or another (genetic imprinting).

The mechanisms for the heritability of the histone state are not fully understood; however, much is known regarding the

mechanism for the heritability of the DNA methylation state during cell division and differentiation. Heritability of the methylation process relies on other enzymes (such as DNMT1) which have a higher affinity for 5-methylcytosine than for cytosine. When this enzyme enters a hemimethylated part of DNA (where 5-methylcytosine is in just one of the two DNA strands), the enzyme can methylate the other component.

While histone adjustments exist throughout the entire chain, the unstructured N-termines of histones (called histone tails) are especially highly modified. Such changes shall involve acetylation, methylation, ubiquitylation, phosphorylation, sumoylation, ribosylation and citrullination. Acetylation is the most researched of all changes. For reference, acetylation of the K14 and K9 lysines of the tail of histone H3 by histone acetyltransferase (HAT) enzymes is known to control transcription in conjunction with complementary histone deacetylases.

One way of thinking is that this propensity of acetylation to be correlated with "successful" transcription is of a biophysical kind. Because it usually has a positively charged nitrogen at the edge, lysine will bind negatively charged DNA phosphates to the spine. The acetylation effect transforms the positively charged amine group to a neutral amide connection on the side chain. It reduces the positive charge, thereby loosening the DNA of the histone. When this happens, complexes such as SWI / SNF and

other transcriptional factors may attach to DNA and cause transcription to occur. That is the "cis" epigenetic role pattern.

In other terms, modifications to the histone tails have a clear impact on the DNA itself.[citation needed] Another epigenetic role concept is the "trans" type. Changes to the histone tails function indirectly on the DNA in this pattern. For eg, lysine acetylation can establish a binding spot for chromatin-modifying enzymes (or transcription machines as well). The chromatin remodeler will then induce chromatin state shifts. In addition, bromodomain – a protein domain that specifically binds acetyl-lysine – is present in several enzymes that help to trigger transcription, including the SWI / SNF complex. This may be that acetylation works in this and the previous manner to facilitate transcriptional activation.

The belief that modifications function as docking modules for similar variables is also borne out by histone methylation.

Methylation of lysine 9 of histone H3 has long been correlated with constitutively silent chromatin (constitutive heterochromatin). Chromodomain (a domain that precisely binds methyl-lysine) in the transcriptionally restrictive protein HP1 has been established to recruit HP1 to K9 methylated regions. One illustration that appears to contradict this biophysical methylation hypothesis is that the tri-methylation of histone H3 at lysine 4 is closely correlated with (and necessary

for full) transcriptional activation. In this case, tri-methylation would introduce a fixed positive charge on the tail.

It has been demonstrated that histone lysine methyltransferase (KMT) is responsible for this methylation process in the patterns of histones H3 and H4. This enzyme requires a catalytically active site named the SET domain (Suppressor of variegation, Enhancer of zest, Trithorax). The SET domain is a 130-amino acid sequence that is active in the regulation of gene expression. This domain has been shown to bind to the histone tail and to induce histone methylation.

Differentiating histone variations are likely to operate in different ways; acetylation at one location is likely to act differently than acetylation at another location. Often, several changes that arise at the same time and can function together to alter the activity of the nucleosome. The concept that numerous complex modifications control gene transcription in a systemic and reproducible fashion is called histone language, while the theory that histone status can be interpreted linearly as a digital knowledge carrier has been mostly debunked. Some of the best-understood mechanisms that orchestrate chromatin-based silencing is the SIR protein-based silencing of the secret mating form loci HML and HMR.

DNA methylation also happens in repetitive sequences and serves to inhibit the production and movement of 'transposable

elements': since 5-methylcytosine may be naturally deaminated (replacing nitrogen by oxygen) to thymidine, CpG sites are frequently mutated and uncommon in the genome, particularly in CpG islands where they stay unmethylated. Thus, epigenetic modifications of this kind have the ability to steer increased rates of irreversible genetic mutation. DNA methylation patterns are reported to be formed and changed in reaction to environmental factors through a dynamic interplay of at least three separate DNA methyltransferases, DNMT1, DNMT3a and DNMT3B, all of which are lethal in mice. DNMT1 is the most common methyltransferase in somatic cells, localizes to the foci of replication, has a 10–40-fold preference for hemimethylated DNA and associates with the proliferating cell nuclear antigen (PCNA).

When ideally altering hemimethylated DNA, DNMT1 passes methylation patterns to a freshly synthesized strand during DNA replication and is thus also referred to as 'maintenance'

methyltransferase. DNMT1 is important for proper embryonic growth, printing and X-inactivation. To attempt to highlight the distinction between this molecular process of inheritance and the traditional Watson-Crick base-pairing system of transmission of genetic material, the word 'Epigenetic tempering' has been used. For fact, for relation to the conservation and dissemination of methylated DNA states, the same idea may be extended to the preservation and

dissemination of variations in histone and also cytoplasmic (structural) heritable systems.

Histones H3 and H4 can also be regulated by demethylation utilizing histone lysine demethylase (KDM). A recently identified enzyme has a catalytically active site named the Jumonji Domain (JmjC). Demethylation happens as JmjC

utilizes several cofactors to hydroxylate the methyl group, thus destroying it. JmjC is capable of demethylating mono-, di-, and tri-methyl substrates.

Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without altering the DNA code. Epigenetic regulation is also correlated with alternate covalent shifts in histones. It is proposed that the consistency and heritability of the states of wider chromosomal regions may require positive feedback as updated nucleosomes employ enzymes that also alter neighboring nucleosomes. A simpler stochastic model for this form of epigenetics can be found here.

It was proposed that chromatin-based transcriptional modulation may be regulated by small RNAs. Small interference RNAs can modulate transcriptional gene expression by epigenetic regulation of selected promoters.

RNA transcripts Once a gene is turned on, it transcribes a compound that (directly or indirectly) retains the function of

that gene. For example, Hnf4 and MyoD promote the transcription of several liver-specific and muscle-specific genes, including their own, via the transcription factor activity of the proteins they encode. RNA signaling entails selective recruitment of the hierarchy of generic chromatin-modifying complexes and DNA methyltransferases to particular RNA loci during differentiation and growth. Many epigenetic modifications are induced by the development of various RNA splice types or by the creation of double-stranded RNA (RNAi).

Descendants of the cell in which the gene was stimulated will retain this behavior, particularly though the initial gene-activation signal is no longer present. These genes are sometimes switched on or off by signal transduction, but in certain systems where syncytia or gap junctions are important, RNA can spread directly to other cells or nucleus through diffusion. A significant volume of RNA and protein is ...