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Introduction to Epigenetics

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Introduction to Epigenetics 1 of 9 Introduction to Epigenetics Watch 1st YouTube: Epigenetics 9:20 minutes https://youtu.be/kp1bZEUgqVI Summary points from 1st YouTube: Epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. The term “epigenetics” has been used since the 1990s, but significant discoveries in 2007 led to its current usage. So epigenetics, which means “above genetics,” is a brand new science, and deals with the various mechanisms involved in gene expression. Gene expression occurs several ways. Adding a methyl group acts like a light switch, and turns genes on or off. Gene expression is also controlled by histones, small proteins that work like a light dimmer knob, changing the degree of expression. Histones are spools that DNA winds around. Histones can tighten or loosen the strand. Loose strands allow more DNA to be read, and tight strands cause less DNA to be read. The DNA is the genome, and may be thought of as the hard drive of our bodies. The epigenome correlates to the computer software, telling the genome what to do. It can change throughout life. Our environment, stress, diet, habits (smoking, alcohol, etc) all can change our epigenome. Most of the epigenetic information of the parent is stripped off a few days after birth, but some of the the parents’ epigenome stays with the offspring. Epigenetic disease information that did not appear in our primitive ancestors is learned and passed down by the epigenetic information from our parents. Watch 2nd YouTube: Epigenetic transformation -- you are what your grandparents 21:14 minutes https://youtu.be/Udlz7CMLuLQ Summary points from 2nd YouTube: 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. 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 2 of 9 of blood vessels, etc., by activating some genes while inhibiting the expression of others. 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. Watch 3rd YouTube: Gene Silencing by microRNAs 4.53 minutes https://youtu.be/t5jroSCBBwk Summary points from 3rd YouTube: MicroRNAs (miRNAs) are members of non-coding RNAs that range in size from 17 to 25 nucleotides. MicroRNAs regulate a large variety of biological functions in plants and animals. As of 2013, about 2000 miRNAs have been discovered in humans (these can be found online in a miRNA database). Each miRNA expressed in a cell may target about 100 to 200 messenger RNAs that it downregulates. Most of the downregulation of mRNAs occurs by causing the decay of the targeted mRNA, while some downregulation occurs at the level of translation into protein. You can inherit from your parents and their parents. Cancer: a variety of epigenetic mechanisms cause different types of cancer. Diabetic wound healing: epigenetic modifications have given insight into the understanding of the pathophysiology of different disease conditions like wound healing in diabetic patients. Stress: is passed on to the next generations by epigenetic tags from parents. Addiction: is a disorder of the brain's reward system which arises through transcriptional and neuroepigenetic mechanisms. Anxiety: is the transgenerational epigenetic inheritance of anxiety-related phenotypes and has been reported in preclinical studies. The transmission of paternal stress- induced traits across generations involved small non-coding RNA signals transmitted via the male germline. Depression: epigenetic inheritance of depression-related phenotypes has also been reported in a preclinical study. Fear conditioning: studies on mice have shown that certain conditional fears can be inherited from either parent. 3 of 9 Other non-coding RNAs sRNAs are small (50–250 nucleotides), highly structured, non-coding RNA fragments found in bacteria. They control gene expression including virulence genes in pathogens and are viewed as new targets in the fight against drug- resistant bacteria.They play an important role in many biological processes, binding to mRNA and protein targets in prokaryotes. (Ted Talks) What you can do to prevent Alzheimer's | Lisa Genova https://youtu.be/twG4mr6Jov0 What Parkinson’s Taught Me | Emma Lawton | TEDxSquareMile https://youtu.be/Hs-vPqfsO0Q The protein folding problem: a major conundrum of science: TED https://youtu.be/zm-3kovWpNQ Genetics and Parkinson's disease | Nervous system diseases | NCLEX-RN | Khan Academy https://youtu.be/FsE3QvWqeqs Specific epigenetic processes include: paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, DNA methylation reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning. https://youtu.be/i9a-ru2ES6Y https://youtu.be/UMFUQkN0ecU 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.[1] The change may be in the pattern of DNA methylation or histone modifications.[2] The allele inducing the change is said to be paramutagenic, while the allele that has been epigenetically altered is termed paramutable.[1] 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.[1] Through proper breeding, paramutation can result in sibling plants that have the same genetic sequence, but with drastically different phenotypes. https://youtu.be/XohX8Ke1maI Bookmarking (also "gene bookmarking" or "mitotic bookmarking") refers to a potential mechanism of transmission of gene expression programs through cell division. 4 of 9 During mitosis, gene transcription is silenced and most transcription factors are removed from chromatin.[1][2] The term “bookmarking” compares transcription to reading from a book. The pause in transcription during mitosis is like closing the book. "Molecular bookmarks" are the factors that allow transcription to resume in an orderly fashion in newborn cells following mitosis (when the book is re-opened). Bookmarks fulfill the following criteria: • at some point prior to the onset of mitosis, the promoters of genes that exist in a transcription-competent state become "marked" in some way, • this "mark" persists both during and after mitosis, and • the marking transmits gene expression memory by preventing the mitotic compaction of DNA at this locus, or by facilitating reassembly of transcription complexes on the promoter, or both. https://youtu.be/3hBoNGozlCo Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. As of 2014, there are about 150 imprinted genes known in the mouse and about half that in humans. Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established ("imprinted") in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.[8] Appropriate imprinting of certain genes is important for normal development. Human diseases involving genomic imprinting include Angelman syndrome and Prader–Willi syndrome. https://youtu.be/J2Y_S4EkLy8 https://youtu.be/5YsTW5i0Xro Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene.[1][2] Gene silencing can occur during either transcription or translation and is often used in research.[1][2] In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and diseases, such as infectious diseases and neurodegenerative disorders. Gene silencing is often considered the same as gene knockdown.[3][4] When genes are silenced, their expression is reduced.[3][4] In contrast, when genes are knocked out, they are completely erased from the organism's genome and, thus, have no expression.[3][4] Gene silencing is considered a gene knockdown mechanism since the methods used to silence genes, such as RNAi, CRISPR, or siRNA, generally reduce the expression of a gene by at least 70% but do not completely eliminate it. Methods using gene silencing are often considered better than gene knockouts since they allow researchers to study essential genes that are required for the animal models to survive and cannot be removed. In addition, they provide a more complete view on the development
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