Abstract
This chapter focuses on epigenetics: the study of stable, often heritable changes that influence gene expression but are not mediated by DNA sequence. These changes play crucial roles in chromatin state regulation which influences processes such as gene expression, DNA repair, and recombination. Evidence demonstrates that epigenetic patterns are altered by environmental factors which are associated with disease risk including diet, smoking, alcohol intake, environmental toxicants, and stress. Studiers have linked environmental pollutants with epigenetic variations particularly changes in DNA methylation, histone modifications, and microRNAs. Growing data have linked epigenetic alterations with heavy metal exposure, organic toxicants, and water chlorination by-products. Studies focusing on the effects of air pollution in humans demonstrate an association between exposure to air pollution and DNA methylation. Several classes of pesticides can modify epigenetic marks, including endocrine disruptors, persistent organic pollutants, arsenic, several herbicides, and insecticides. This chapter explores epigenetics.
TopChapter Outline
11.1 The Epigenome and Epigenomics
11.2 Epigenetic Mechanisms
11.2.1 Regulation at the DNA Level
11.2.3 Regulation at the Transcription Level
11.2.4 Regulation at Post-Transcription Level
11.2.5 Regulation by non-coding RNAs
11.3 Epigenetics, Environment and Disease
11.3.1 Physical Activity, Cancer, Diet and Chronic Diseases
11.3.2 Heavy Metals
11.3.3 Organic Toxicants
11.3.4 Air Pollution
11.3.5 Pesticides
Chapter Summary
TopLearning Outcomes
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Define epigenetics and epigenomics
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Explain the various epigenetic mechanisms
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Summarize the effects of lifestyle habits and environmental pollutants in gene expression and disease.
Top11.1 The Epigenome
Epigenetics is the study of stable, often heritable changes which influence gene expression but are not mediated by DNA sequence. These changes play crucial roles in chromatin state regulation which influences processes such as gene expression, DNA repair, and recombination (Berger et al., 2009). The most distinctive aspects of epigenetics are that these changes in expression occur without a change in the original sequence of the DNA which is the arrangements of the adenine, cytosine, guanine, and thymine (ACGT) bases that constitute specific genes (Robinson, 2016). The term “epigenomics” was coined to describe all of the chemical modifications that are added to the genome to regulate gene expression and activity. Epigenetic changes are inheritable, modifiable, or erasable in response to developmental cues or external and environmental stimuli. A better understanding of the epigenomic factors that contribute to many disease processes will lead to additional strategies for treatment in the future. For example, defects in epigenetic regulation have been linked to developmental defects, metabolic disorders and cancer in humans. The connection between the epigenome and more common complex diseases including psychosis, diabetes and asthma are also being discovered. (Murrell et al., 2005; Berger et al., 2009; Fingerman et al., 2013)
Key Terms in this Chapter
Nanotechnology: Field of research designed for the implementation of nanomaterials for new biological or biochemical applications.
Alternative Splicing: A phenomenon of splicing that results in different options or patterns for a given gene; a process mediated by introns, exons, and proteins that increases the complexity of gene expression.
Insulator/Insulator Protein: A group of elements found between the enhancer and the promoter.
Silencers: Specific sequences upstream of the promoter region that prevent RNA polymerase from binding to the promoter, thus curtailing gene transcription.
Imprinting: A phenomenon where of the two inherited copies of each gene (alleles), one of them is silenced by epigenetic processes such that only one of them (either from mother or father) is expressed.
Enhancesome: A type of enhancer containing multiple sites for activator binding.
Splicing Regulatory Elements: Elements of gene expression between transcription and translation that play a role in protein processing and degradation.
Particulate Matter: The mixture of solid and liquid particles suspended in the air.
Persistent Organic Pollutants: Toxic organic chemicals that are resistant to environmental degradation and that persist and accumulate in adipocytes of living organisms.
Epigenetics: The study of changes in an organism that influences gene expression but are not mediated by the original DNA sequence.
Biotin (Vitamin B7): A vitamin B-complex that aids in carbohydrate and fat metabolism and in fatty acid and glucose synthesis.
Nicotinamide Adenine Dinucleotide: An important electron carrier involved in various redox reactions of living systems—for example, aerobic respiration.
Positive Gene Regulation: Gene regulation that results in increased enzymatic activity in the presence of product; in contrast to negative gene regulation.
Phytochemicals: Biologically active chemicals present in plants that play a role in human health and disease.
Insecticides: A pesticide used to harm, kill or repel insects.
Endocrine Disruptor: Exogenous chemicals that alter or interfere with the body’s normal endocrine function, thus further impairing homeostasis.
Herbicides: A pesticide used to kill unwanted vegetation.
Small Ubiquitin-Related Modifier (SUMO): A polypeptide of less than 100 amino acids that attach or detach to other proteins to modify their functions.
Genome-Wide Analyses: The process of measuring and identifying gene features of entire genomes.
Epigenomics: The identification of the complete set of epigenetic modifications implicated in gene expression.
Chromatin Remodelling: Regulated modification of chromatin to allow DNA to be compressed into the nucleus of a cell.
Competitive DNA Binding: A competition to bind DNA when there is overlap between enhancer and silencer sequences.