Epigenetics and Neurogenesis
“Epigenetics” is defined as to study the mechanisms which include DNA and histone modifications that lead to change in the expression of genes or cellular phenotype without aleration in the primary sequence of the DNA. These modifications are having a heritable pattern of gene expression in nature. Commonly studied epigenetic marks referred as DNA methylation and histone modifications include acetylation, ubiquitination, sumolyation, phosphorylation and others. These epigenetics marks leads to change in the protein or DNA in such a way that help in the transcriptional active of particular sets of gene locus required in specific cellular function or differentiation. Epigenetics mechanisms now emerged or recognized as master regulators in the process of neurogenesis especially in adult neurogenesis.
1. Epigenetic modification of Histone
The building blocks of mammalian chromatin i.e. nucleosome core, consists of approximately 147 bp of DNA wrapped around two copies of distinct histone proteins: H2A, H2B, H3 and H4 (Lugar et al., 1999). Generally loosely structured N-terminal tail of histones which protrude out from the nucleosome core undergo at least six different post translational modifications namely acetylation, ubiquitination, methylation, phosphorylation, ribosylation and SUMOylation (.(Kouzarides, 2007; Delcuve et al., 2009). Theses epigenetic modification of histone leads to alteration of chromatin condensation and thereof become more accessible for recruitment of several transcription factors that help in gene expression. These are known as “Histone Code” (Bernstein et al., 2007).
Histone acetylation and deacetylation: One of the important histone modifica...
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...in the adult (Shahbazian et al., 2002) and it was observed that MeCP2 deficiency leads to altered gene expression and delayed neuron maturation (Smrt et al., 2007). It was also reported that MeCP2 overexpression inhibits astroglial but promotes neuronal differentiation in vito and in vivo (Tsujimura et al., 2009). Very recently it was found that Growth arrest and DNA damage inducible protein 45 beta (GADD45b) express in adult dentate gyrus and regulates activity induced adults neurogenesis by promoting demethylation of target genes critical for the process including BDNF and FGF (Ma et al., 2009). Thus, GADD45b induced DNA demetylation of which leads to epigenetic changes target genes that help in the maintenance of progenitor cells. Therefore, a flood of literatures are evident that epigenetic regulation is a master regulator of neurogenesis and related disease.
The MECP2 gene makes a protein, also called MECP2, believed to play a pivotal role in silencing, turning off or regulating the activity of other genes. The MECP2 mutation (change in the gene) causes the turn-off/regulatory mechanism to fail, allowing other genes to function abnormally(Rett Syndrome - NORD). Rett syndrome is a genetic disorder of developmental failure of brain maturation. This is thought to occur when subsets of neurons and their connections are disrupted during a dynamic phase of brain development. This deviation occurs at the end of pregnancy or in the first few months of life during the critical phases of synapse development. How mutations in MeCP2 lead to Retts is not well understood but is the focus of intense research.
Histone modification may or may not be dependent on DNA methylation and is difficult to detect compared to LOH.
Trisomy 13 or Patau Syndrome” Trisomy 13 is a genetic disorder found in babies. It is also called Patau syndrome in honor of the physician who first described it, Krause Palau. Trisomy 13 is a genetic disorder in which there is three copies of chromosomes on Chromosome 13. Patau first described the syndrome and its involvement with trisomy in 1960. It is sometimes called Bartholin-Patau syndrome, named in part for Thomas Bartholin, a French physician who described an infant with the syndrome in 1656.
Hypermethylation of CpG islands at tumor suppressor genes turns them off, while hypomethylation leads to the instability and inappropriate activation of oncogenes and transposable elements. Methylation can be directly related to genetic mutations, an example of this case is methylated cytosine. Methylated cytosine mutates spontaneously in vivo through deamination to give thymine. According to Andy Bannister (n.d.), “37% of somatic p53 mutations and 58% of germ line mutations occur at methylated...
Biologist, Gregor Johann Mendel, discovered how traits passed from one generation to the next. Mendel studied and used pea plants to discover the principles that rule heredity. He found that each parent, father, and mother pass down traits to their offspring, who inherit different combinations of their recessive or dominant alleles-terms introduced by Mendel during the 19th century. Mendel introduced important principles teaching us that recessive traits will only be shown in the phenotype if both alleles are recessive. Mendel’s laws of inheritance include the Law of segregation and the Law of independent assortment.
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.
...d up in lysosomes of the amyloid precursor protein (APP). Once broken, in an improper process, into toxic peptides which are associated with Alzheimer's Disease, researchers suggest they are perhaps a reason for the development of Alzheimer’s disease. Within weeks of using gene therapy to increase the activity of the NEU1 enzyme, it was found that plaque began to decline. The regions in which the researchers saw a decline in plaque was in the hippocampus.
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.
Ongoing studies suggest there could be a correlation to malfunctioning genes that produce significant chemicals in the brain, which are responsible for the d...
Distinct characteristics are not only an end result of the DNA sequence but also of the cell’s internal system of expression orchestrated by different proteins and RNAs present at a given time. DNA encodes for many possible characteristics, but different types of RNA aided by specialized proteins sometimes with external signals express the needed genes. Control of gene expression is of vital importance for an eukaryote’s survival such as the ability of switching genes on/off in accordance with the changes in the environment (Campbell and Reece, 2008). Of a cell’s entire genome, only 15% will be expressed, and in multicellular organisms the genes active will vary according to their specialization. (Fletcher, Ivor & Winter, 2007).
Meiosis is a specialized form of nuclear division in which there two successive nuclear divisions (meiosis I and II) without any chromosome replication between them. Each division can be divided into 4 phases similar to those of mitosis (pro-, meta-, ana- and telophase). Meiosis occurs during the formation of gametes in animals.
A recent field of biology, called epigenetics, is rapidly transforming previous ideas on the impact of genes. The...
The scientific and medical progress of DNA as been emense, from involving the identification of our genes that trigger major diseases or the creation and manufacture of drugs to treat these diseases. DNA has many significant uses to society, health and culture of today. One important area of DNA research is that used for genetic and medical research. Our abi...
...e in the neurodevelopment cycle, such as increased neuronal dysfunction with decreased connectivity and increases in loss of neuropril and extrinsic factor like substance abuse, developmental stress, relationship problem(Elder, Evans and Nizette, 2007).