Biological Sciences
Epigenetic Changes
Epigenetic changes refer to alterations in gene expression that do not involve changes to the underlying DNA sequence. These changes can be influenced by environmental factors and can have a significant impact on an organism's development and health. Examples of epigenetic changes include DNA methylation, histone modification, and non-coding RNA regulation.
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10 Key excerpts on "Epigenetic Changes"
eBook - ePub- (Author)
- 2019(Publication Date)
- Academic Press(Publisher)
Chapter 1Basics of epigenetics: It is more than simple changes in sequence that govern gene expression
Shilpy Sharma; Osama Aazmi Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Pune, IndiaAbstract
It is a widely accepted fact that distinction between species is defined not only by the ensemble of its genes but also more critically by how these genes are regulated such that the expression profiles change over space and time. Two major factors that determine gene expression and, in fact, a particular state of a functional cell, include genetics, the study of heritable changes in the nucleotide sequences, and epigenetics, the study of mitotically and/or meiotically heritable alterations in gene expression that are not associated with changes in the underlying DNA sequences. Here, we provide an overview about the major epigenetic mechanisms including DNA methylation, histone posttranslational modifications, chromatin modifications, and noncoding RNAs (including miRNAs and lncRNAs) that govern changes in gene expression that are actually dependent on the environment and not on the underlying gene sequence. These mechanisms are potentially reversible and play crucial roles in regulating normal growth and differentiation. Alteration in the epigenetic marks have often been linked with different disease processes; and several attempts have been made to use these epigenetic modifications as a biomarker for the identification of individuals at risk and/or suffering from a disease condition using minimally invasive techniques. Additionally, the reversible nature of these epigenetic marks offers an attractive target for therapy, and hence, several drugs that target epigenetic factors and/or the linked pathways are currently being developed and/or tested in clinical trials. These topics have been extensively discussed through the length of this chapter.
No longer available |Learn more- (Author)
- 2014(Publication Date)
- Research World(Publisher)
________________________ WORLD TECHNOLOGIES ________________________ Chapter- 5 Epigenetics In biology, and specifically genetics, epigenetics is the study of heritable changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi-(Greek: επί - over, above) -genetics . These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations. However, there is no change in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or express themselves) differently. The best example of Epigenetic Changes 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, a single fertilized egg cell – the zygote – changes into the many cell types including neurons, muscle cells, epithelium, blood vessels etc. as it continues to divide. It does so by activating some genes while inhibiting others. ________________________ WORLD TECHNOLOGIES ________________________ Etymology and definitions Epigenetic mechanisms Epigenetics (as in epigenetic landscape) was coined by C. H. Waddington in 1942 as a portmanteau of the words genetics and epigenesis . Epigenesis is an old word which has more recently been used to describe the differentiation of cells from their initial totipotent state in embryonic development. When Waddington coined the term the physical nature of genes and their role in heredity was not known; he used it as a conceptual model of how genes might interact with their surroundings to produce a phenotype. Robin Holliday defined epigenetics as the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms.
eBook - PDF- Saura C. Sahu(Author)
- 2012(Publication Date)
- Wiley(Publisher)
The term ‘epigenetics’ was coined by Conrad Hal Waddington, incorporating the concept of ‘epigenesis’ (undifferentiated cells increase in complexity as development progresses) with ‘genetics,’ to describe the complex genetic and biological programs that unravel during embryonic development (Waddington, 1956). These programs, based on (i) the underlying genetic information and (ii) intercellular and intracellular communication, cause cells to differentiate into determinate tissues and organs, and eventually result in a complex living organism. Robin Holliday Toxicology and Epigenetics , First Edition. Edited by Saura C. Sahu. c 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd. 74 Toxicology and Epigenetics broadened the definition of epigenetics to describe DNA methylation changes that are inherited through cellular division and passed along to the next generation through germline cells (Holliday, 1987). In 1975, two studies (Holliday and Pugh, 1975; Riggs, 1975) independently described DNA methylation and its probable importance in differentiation, regulation, imprinting, and development. Since then, many more mechanisms of DNA modification and control of gene expression have been discovered. The other well-known Epigenetic Changes encompass gene expression and phenotypic changes brought about by histone modifications and small non-coding RNA molecules. Other novel mechanisms continue to be discovered. 5.2 Mechanisms of molecular Epigenetic Changes Three types of known molecular Epigenetic Changes include DNA methylation, histone modifications, and small non-coding RNAs that regulate gene expression (Figure 5.1).
eBook - PDF- Deborah K. Hansen, Barbara D. Abbott(Authors)
- 2008(Publication Date)
- CRC Press(Publisher)
4 Epigenetic Mechanisms: Role of DNA Methylation, Histone Modifications, and Imprinting Robert G. Ellis-Hutchings and John M. Rogers Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, U.S.A. INTRODUCTION TO EPIGENETICS The primary DNA sequence is only a foundation for understanding how the genetic program is read. Superimposed upon the DNA sequence is a layer of heritable “epigenetic” information, a facet of the genetic code that we have only just begun to discover and appreciate. Epigenetics is defined as “mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence” (1). This epigenetic information is stored as chemical modifications falling into two main categories: (1) DNA methylation and (2) changes to the histone proteins that package the genome (2). By regulating DNA accessibility and chromatin structure, these chemical changes influence how the genome is translated across a diverse array of developmental stages, tissue types, and disease states (3–5). In this chapter, we will first discuss key features of the DNA methylation and histone protein modification landscapes, including structural and chemical char-acteristics of DNA methylation and histone protein changes, the enzymes involved in such changes, and the effects of such modifications on gene transcription. We will also discuss the interplay of these dynamic modifications and the emerging role of small RNAs in epigenetic gene regulation. Epigenetic modifications are 93 94 Ellis-Hutchings and Rogers particularly dynamic within the complex regulatory environment controlling proper development; therefore, a substantive component of this chapter will focus on epigenetic regulation during development.
- Peter C. M. Molenaar, Richard M. Lerner, Karl M. Newell, Peter C. M. Molenaar, Richard M. Lerner, Karl M. Newell(Authors)
- 2013(Publication Date)
- The Guilford Press(Publisher)
However, neither the epigenetic mechanisms nor the dynamics of developmental processes are taken into account in the recent studies on evolution and development. The totality of research findings gives no support to the neo-Darwinian theory of evolution by the natural selection of random genetic mutations, nor to any theory ascribing putative differences in human attributes predominantly to genes. The over- whelming determinants of health and behavior are social and environmental. Heredity is distributed over the seamless web of nested organism–environment interrelationships extending from the social and ecological to the genetic and epigenetic. Consequently, CHAPTER 5 132 EPIGENETIC DEVELOPMENT AND EVOLUTION there is no separation between development and evolution, and the organism actively participates in shaping its own development as well as the evolutionary future of the entire ecological community of which it is part. “Epigenetic” Then and Now The term epigenetic, as used today in epigenetic inheritance, refers to effects that do not involve DNA base sequence changes, but only the chemical modifications of DNA or histone proteins in chromatin (complex of DNA and protein that make up chromo- somes in the nucleus of cells) that alter gene expression states. Epigenetic inheritance has been defined (Bird, 2007, p. 398) as “the structural adaptation of chromosomal regions so as to register signal or perpetuate altered activity states.” But such a defini- tion is rapidly becoming obsolete (Ho, 2009a, 2009b, 2009c, 2009d, 2009e, 2009f, 2009g). In reality, epigenetic modifications encompass a great variety of mechanisms. They act during and after transcription, and at translation of genetic messages; they can even rewrite genomic DNA (see Ho, 2009c). Hence the distinction between genetic and epigenetic is increasingly blurred.
eBook - PDFGenomics
Fundamentals and Applications
- Supratim Choudhuri, David B. Carlson, Supratim Choudhuri, David B. Carlson(Authors)
- 2008(Publication Date)
- CRC Press(Publisher)
Counting 122 3.5.5.2. Choice 122 3.5.6. Pseudoautosomal Regions Escape Inactivation 123 3.6. Epigenetics of Disease and the Scope of Epigenetic Therapy 124 4. CONCLUSION 124 REFERENCES 125 1. INTRODUCTION The term “epigenetics” was coined by Conrad Waddington in 1942. Historically, the term has been used with different meanings under different contexts. In the context of molecular biology, epigenetics can be defined as the study of mitotically or meiotically heritable changes in gene function that cannot be explained by changes in the DNA sequence (1). The collection and the combination of all epigenetic factors (epigenome) provide information about the spatial and organizational constraints of the genome that complement genetic instructions to influence the outcome of genome expression. Epigenetic inheritance involves the transmission of information (epigenetic mark) not encoded in DNA, from parent cell to daughter cells and from generation to generation. Epigenetic mark is like a bookmark that flags the chromatin state, “on” or “off”, “open” or “closed”, so that they can be identified and maintained in the daughter cells. In the spirit of genomics, the term “epigenomics” has come into existence and is often used synonymously with the term “epigenetics”. However, epigenomics is a new frontier that studies Epigenetic Changes at the level of the entire genome (2). At the present moment, any discussions on epigenomics and epigenetics are invariably intertwined. 2. MOLECULAR BASIS OF EPIGENETIC REGULATION Factors that chemically modify DNA without altering the sequence may alter chromatin conformation, modulate the accessibility and binding of the transcription machinery, and influence genetic regulatory cross-talk. Since all these events have downstream effects on transcription, they may trigger an epigenetic effect.
eBook - ePubOsteoporosis
A Lifecourse Epidemiology Approach to Skeletal Health
- Nicholas C Harvey, Cyrus Cooper, Nicholas C Harvey, Cyrus Cooper(Authors)
- 2018(Publication Date)
- CRC Press(Publisher)
17 ).Epigenetic mechanisms include DNA methylation, histone modifications and non-coding RNAs (ncRNAs), as shown in Figure 7.1 (5 ,18 –20 ).Figure 7.1The coding and structural information superimposed the base sequence of DNA is organised in multiple epigenomes, which differ according to cell and tissue type. DNA methylation at cytosine adjacent to guanine bases (CpG sites), in addition to the covalent modifications of histone tails and histone variants, can contribute information to nucleosomal remodelling machines. (Nucleosomes are a subunit of DNA packaging composed of eight histone protein cores forming a complex around which DNA is wrapped.) Through nucleosome remodelling, leading to ravelling and unravelling of DNA, genes and loci encoding non-coding RNAs become susceptible to transcription. Transcription factors (not shown in this diagram) also play a major part in the competence and organisation of the genome. (Reproduced with permission from Jones et al., Nature . 2008;454(7205):711-5.)Post-translational histone modificationsPost-translational histone modifications and the accompanying histone-modifying enzymes form a major part of the epigenetic regulation of genes. DNA is wrapped around an octamer of four different histone molecules (H2A, H2B, H3 and H4) to form a nucleosome, the basic unit of chromatin. The flexible N-terminal tails of core histones that protrude from the nucleosome undergo various post-translational modifications, including acetylation, methylation, phosphorylation, ubiquitination, sumoylation, ADP ribosylation, deamination and noncovalent proline isomerization (21 ). The patterns of histone modifications alter the transcriptional accessibility of the chromatin. It has been shown that euchromatin, a more relaxed, actively transcribed state of DNA, is characterized by high levels of acetylation and trimethylated (H3) lysine residues (K-number) on specific histones H3K4, H3K36 and H3K79, while low levels of acetylation and high levels of H3K9, H3K27 and H4K20 methylation are indicative of a more condensed, transcriptionally inactive heterochromatin (22
eBook - PDF- Vikas Mishra(Author)
- 2019(Publication Date)
- Delve Publishing(Publisher)
In differentiated cells, signals fine-tune cell functions through changes in gene expression across the lifespan. A flexible epigenome allows us to adjust to changes in the world around us, and to “learn” from our experiences. In many ways, epigenetic expression can be thought of as the “software” of the genome and directs embryogenesis and development, as well as influences the development of an individual’s body and brain after birth. Unique sets of genes are induced or silenced epigenetically during different stages of life and these are responsible for the development and maturation of the individual through orchestrated events in combination with input from the environment. Any kind of epigenetic factors influencing genes or gene expression networks during life stages can result in an imbalance in the regulation process, and might have a life-long effect on the individual. Epigenetics Across the Human Lifespan 57 While such flexibility gives rise to beneficial adaptability to environmental conditions, it likewise allows weaknesses to integrate and exert negative and diseased outcomes on both individual and evolutionary scales. We have used data from human studies in most cases in this review, but in some cases where such data is sparse or unavailable, we have supported our explanations with data from studies on rodent and/or other animal models. From the Periconceptional Environment to Birth For most genes, total reprogramming is necessary very soon after conception in order to start with an epigenetic “clean slate,” which then allows all of the specialized cells derived from the egg and sperm to develop with stable cell-specific gene expression profiles and remain properly differentiated. This happens in the fertilized egg: global DNA demethylation is followed by remethylation to reprogram the maternal and paternal genomes for efficient gene expression regulation.
eBook - PDFMeaning Of Life And The Universe: Transforming
Transforming
- Mae-wan Ho, Peter T Saunders(Authors)
- 2017(Publication Date)
- World Scientific(Publisher)
In the post-genomics era, an increasing number of geneticists have begun to take notice of non-Mendelian inheritance and its invalidation of the basic tenets of biometrical genetics. In a paper published in Behavioral and Brain Sciences , Evan Charney at Duke University speaks of a “paradigm shift” in the science of genetics. He points to recent discoveries of numerous processes that create extensive mutations in genome sequences and structure, as well as epigenetic modifications, which are com -pletely at odds with the Mendelian model of inheritance underpin-ning heritability estimates. 26 Individuals do not have genes that are immutable throughout life, nor do they have the same genes in every cell of the body. He highlights retrotransposons — jump-ing genes that replicate and integrate themselves into different sites in the genome — which alter the sequence and state of activ-ity of many genes; copy number variation and chromosomal abnormalities (aneuploidy) similarly, occur frequently in somatic cells as well as germ cells, both as part of normal development and in response to noxious environmental stimuli. Different tis -sues show distinctly different propensity for change, brain cells being especially prone to such modifications. These add to the already large repertoire of epigenetic processes that modify genes in response to environmental stimuli, 4,12,32–34 and most notably in the brain. 37 The fundamental assumption of twin studies — that monozy-gotic twins share 100% of their genes — is demonstrably false. No Genes for Intelligence in the Fluid Genome 183 MZ twins differ, to begin with, in the mitochondrial DNA (mtDNA) complement allocated in cell division of the original oocyte that generated the twins. The oocyte may have had different sets of mtDNA, a condition referred to as heteroplasmy. MZ twins diverge substantially in epigenetic modifications as well as retro-transposition, copy number variations and aneuploidy through-out life.
eBook - PDFGene Expression and Regulation in Mammalian Cells
Transcription Toward the Establishment of Novel Therapeutics
- Fumiaki Uchiumi(Author)
- 2018(Publication Date)
- IntechOpen(Publisher)
The regulation of histone modifications is a balance between its epigenetic writers and epigenetic erasers , and the dysregulation of either would result in aberrant histone modifications and thus a change in the transcription. The group of proteins that are Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics 96 involved in interpreting these histone marks, epigenetic readers , are also crucial, whose dys-regulation could result in the misinterpretation of the epigenetic marks and therefore a change in transcriptional landscape. A point to note is only a subset of these residues can undergo multiple modifications. For exam -ple, lysine 27 on histone 3, can be either acetylated (in active enhancers) or tri-methylated (a mark of repressed promoters), each of which contributes to a different transcriptional outcome. It is also hypothesized that the addition of a particular covalent modification sterically inhibits the alternate modification. Additionally, histone marks on the enhancers such as H3K4me and H3K27ac are capable of regulating the 3D structure of chromatin. Since this method of regula -tion is indeed another layer that the cell regulates gene expression in a normal setting, it comes as no surprise that chromatin modifiers are known to be dysregulated in cancer, resulting in the aberrant expression of its downstream genes (lysine acetyltransferases (KATs) reviewed in [ 8], histone methyltransferases (HMTs) reviewed in [ 9 ], histone deacetylases (HDACs) reviewed in [10–12], histone demethylases reviewed in [13, 14 ]). Here, we will focus on epigenetic factors which are dysregulated in cancer, resulting in a transcriptional change.
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