An epigenetic mechanism refers to any heritable influence (in the progeny of cells or individuals) on chromosome or gene function that is not accompanied by a change in DNA sequence (Yoder et al 1997); a change in phenotype without a change in genotype. These changes may last through generations of cell divisions. Although it was once thought that there was no new generation of neurons in the nervous system, studies have shown that the brain retains neural stem cells (NSCs) into adulthood, and neurogenesis continues to occur. Neural stem cells (NSCs) are the initial cells found in the nervous system and differentiate into the main cell types: oligodendrocytes, astrocytes and neurons. There are three epigenetic mechanisms which are involved in each of these differentiations; these are DNA methylation, histone modifications and noncoding ribonucleic acid (ncRNA) expression, which lead to activating and silencing the correct genes at each step. Epigenetic mechanisms have been implicated play a huge role in several functions in the nervous system such as in neurogenesis, neuronal- glial differentiation and also have roles in higher functions such as memory and cognition. A major mechanism in epigenetics is DNA methylation. DNA methylation occurs in two mechanisms and is the addition of a methyl (-CH₃) group through a covalent bond to a cytosine side chain. DNA methylation is catalysed by a group of enzymes called DNA methyltransferases (DNMTs). DNMT adds methyl groups to cytosine residues. Cytosines have to be immediately followed by a Guanine In order to be methylated, these are called CpG dinucleotides. Around 70% of these dinucleotides get methylated whilst the rest are in clusters called CpG islands. There are two typ... ... middle of paper ... ...Glass, Non-coding RNAs as regulators of gene expression and epigenetics, 2011, oxford journals, 90 (3), p430-440 J. David Sweatt. (2009). Experience-dependent Epigenetic Modifications in the CNS. Biol Psychiatry. 65 (3), 191-197. Chwang WB, O'Riordan KJ, Levenson JM, Sweatt JD. ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem. 2006;13:322–328 Kaili Anier, Anti Kalda, epigenetics in the nervous system. Learn Mem. 2006; 43-72 Atd Bio, Epigenetics, 2013, Feng. J. Chang, H. Li E., Fan G. Dynamic expression of de novo DNA Methyltransferases DNMT3a and DNMT3b in the central nervou system. J Neruoscience Res, 2006 (79), p734-746 Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 2004;42:961-72
Hippocampus is a small, curved region, which exists in both hemispheres of the brain and plays a vital role in emotions, learning and acquisition of new information. It also contributes majorly to long term memory, which is permanent information stored in the brain. Although long term memory is the last information that can be forgotten, its impairment has become very common nowadays. The dysfunction is exemplified by many neurological disorders such as amnesia. There are two types of amnesia, anterograde and retrograde. Anterograde amnesia is inability in forming new information, while retrograde refers to the loss of the past memory. As suggested by Cipolotti and Bird (2006), hippocampus’s lesions are responsible for both types of amnesia. According to multiple trace theory, the author suggests that hippocampal region plays a major role in effective retrieving of episodic memory (Cipolotti and Bird, 2006). For example, patients with hippocampal damage show extensively ungraded retrograde amnesia (Cipolotti and Bird, 2006). They have a difficult time in retrieving information from their non-personal episodic events and autobiographical memory. However, this theory conflicts with standard model of consolidation. The difference between these theories suggests that researchers need to do more work to solve this controversy. Besides retrieving information, hippocampus is also important in obtaining new semantic information, as well as familiarity and recollection (Cipolotti and Bird, 2006). For instance, hippocampal amnesic patient V.C shows in ability to acquire new semantic knowledge such as vocabularies and factual concepts (Cipolotti and Bird, 2006). He is also unable to recognize and recall even...
Miller, Kenneth R. and Joseph S. Levine. “Chapter 12: DNA and RNA.” Biology. Upper Saddle River: Pearson Education, Inc., 2002. Print.
Histone modification may or may not be dependent on DNA methylation and is difficult to detect compared to LOH.
The epigenome marks the genome, determining whether or not a gene is expressed and if so, to what level. It does this in two ways, DNA methylation, and histone modification. DNA methylation is where a methyl group, a tag of carbon and hydrogen, connects to a part of DNA (to the gene) and decides for it to be expressed or not. Histone modification is where a chemical tag secures a histone, or a protein, and tightens or loosens the gene's coil around it to determine how greatly the gene is expressed.
The majority of brain development occurs during the first few years of life. Although genetics provide the basic blueprint for the brain, one’s experiences lay the foundation for future interactions, health, learning, and behavior. Developing the capacity and resources to cope with stress is a significant part of a child’s early development (Felitti et al., 1998 and Anda et al., 2006).
Spiers, H., & Bendor, D. (2014). Enhance, Delete, Incept: Manipulating hippocampus-dependent memories. Brain Research Bulletin,
McEwen, B. (1999). Stress and hippocampal plasticity. (Vol. 22, pp. 105-122). New York,NY: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University. Retrieved from http://www.annualreviews.org/doi/abs/10.1146/annurev.neuro.22.1.105
DNA methylation is catalyzed by the enzyme: DNA methyl trasnferase (DNMTs). Methylation of DNA segments leads to the silencing of transposable elements. Hence this mechanism is repressive to transcription, by that enhancing genomic stability. However, there exist “CpG” islands that are associated with gene promoters that escape methylation hence stability.
Almost all biology students learn the fundamentals of gene expression, DNA contains information which is transcribed into RNA to create protein. Students however, are not taught of RNA Interference, the biological process where RNA molecules inhibit a gene’s expression, RNAi for short. While RNAi is a fairly new discovery, its use in modern biological research is groundbreaking. RNA Interference works by binding Double-stranded RNA molecules (siRNA) to a complementary messenger RNA. The enzymes Dicer and Slicer then cleave the chemical bonds which hold the messeger RNA in place and prevent it from delivering protein silencing instructions thus, the term, Gene Silencing. This phenomenon was first discovered by Richard Jorgensen in 1990 when he was trying to produce deeper purple colored petunias by introducing more purple pigment genes to the flower. To his surprise, the purple petunia turned completely white and got the opposite of his predicted result. At the time Jorgensen coined this effect, “Cosuppression”. It was not until 1998 that Andrew Fire and Craig, C Mello explained the process of RNAi and discovered its use in Caenorhabditis elegans (C. Elegans). In 2006 Fire and Mello won the Nobel Prize in Physiology or Medicine “for their discover of RNA Interference – gene silencing by double stranded RNA”. They utilized the nematode, C. Elegans due to its whole genome being sequenced. This unique characteristic allows for every gene to be tested
Zhao X, Su J, Wang F, Liu D, Ding J, et al. (2013) Crosstalk between NSL Histone Acetyltransferase and MLL/SET Complexes: NSL Complex Functions in Promoting Histone H3K4 Di-Methylation Activity by MLL/SET Complexes. PLoS Genet 9(11): e1003940. doi:10.1371/journal.pgen.1003940
Epigenetics is the word that is used for genes that are modified in order to assist certain genome sequences that lead to diseases and disorders. Epigenetics has come a long way since the first genome sequence had its draft breakthrough in the year 2000 (NOVA 2012). From depression to cancer, epigenetics has made its way through to provide families with the appropriate knowledge and perhaps medication in order to avoid these diseases and disorders in the future.
Weaver, I.C.G., Meaney, M.J. & Szyf, M. (2006).Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proceedings of the National Academy of Sciences, U.S.A., 103.
Epigenetics is the study of both heritable and non-heritable changes in gene translation, which do not stem from mutation. Epigenetic alterations to DNA may occur in several different ways; histone modification, DNA methylations, expression of microRNAs, and changes of the chromatin structure (Ntanasis-Stathopoulos et al). Depending on their presentation, they may be passed on to offspring. The exact mechanism of heritable epigenetic modification has not been discovered, but all of these alterations may have some impact on a wide range of disorders and have far reaching implications in the medical field. The study of epigenetics seeks to answer the age old question of whether nature or nurture is responsible for our phenotype, and it has arrived at the answer that in fact, both are. The discovery of epigenetic changes may lead us to cure many disorders, and even personality problems.
As the human body goes through different experiences, the brain grows, develops, and changes according to the environmental situations it has been exposed to. Some of these factors include drugs, stress, hormones, diets, and sensory stimuli. [1] Neuroplasticity can be defined as the ability of the nervous system to respond to natural and abnormal stimuli experienced by the human body. The nervous system then reorganizes the brain’s structure and changes some of its function to theoretically repair itself by forming new neurons. [2] Neuroplasticity can occur during and in response to many different situations that occur throughout life. Some examples of these situations are learning, diseases, and going through therapy after an injury.
The MTHFR enzyme is required for methylation. In the article, Methylation Problems Lead to 100s of Diseases, it is stated that “Methylation is the process of taking a single carbon and three hydrogens, known as a methyl group, and