1. Histone modifications can effect transcription by altering the chromatin structure or the interaction with other regulatory proteins. Addition of positive or negative charges through the modifications disrupts the electrostatic interaction between the histones and DNA, which modulates the chromatin structure and therefore, the accessibility of DNA to the regulatory proteins. DNA methylation is an epigenetic modification which can influence the interaction between transcription factors and CpG dinucleotides, chromatin structure or binding between methylated DNA and methylation recognition factors.
The different types of histone modifications are :
Acetylation is mediated by histone acetyltransferases (HATs) which act as coactivators for transcription by interacting with the DNA-binding activators. Acetylation catalyzes the transfer of an acetyl group to the ε-amino group of the lysine residue with the utilization of the acetyl CoA as cofactor.Example: H3K56 acetylation by p300/CBP. HDACs have opposite effects to that of HATs, and remove the acetyl group from the lysine residues.
Phosphorylation is mediated by kinases by the transfer of phosphate group to the hydroxyl group of the amino-acid side chain of the histones from ATP, and can be play activatory or repressive role. This results in the addition of negative charge to the histones, thereby effecting the chromatin structure. Example: Phosphorylation of H3 on Ser 10 is associated with transcriptional activation. H2A phosphorylation by MSK1 represses transcriptional activation. Phosphatases revert back the effect of kinases by removing the phosphate group.
Methylation of the histones by methyltransferases occurs at the lysine or arginine residues, which can undergo mono-, di...
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...evel of transcript, protein synthesis or genome.
The effects of RNAi can be contrary to chromatin and DNA modifications in mediating mRNA degradation, inhibition of translation, DNA elimination and similar in heterchromatin formation.
RNAi is post-transcriptional, histone modification can be transcriptional and post-translational modification and DNA modification is at the level of transcription.
RNAi can be reversible or irreversible, while histone and DNA modifications are reversible process.
RNAi involves complementary base-pairing with the target RNA to bring about repression, while DNA and chromatin modification requires bromodomains, chromodomains, specific amino-acid residues and chemical groups for protein- DNA and -histone interaction.
RNAi, DNA and chromatin modification are involved in heterochromatin formation and gene regulation and genome stability.
Miller, Kenneth R. and Joseph S. Levine. “Chapter 12: DNA and RNA.” Biology. Upper Saddle River: Pearson Education, Inc., 2002. Print.
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.
Gene expression is the ability of a gene to produce a biologically active protein. This process is regulated by the cells of an organism, it is very important to the survival of organisms at all levels. This is much more complex in eukaryotes than in prokaryotes. A major difference is the presence in eukaryotes of a nuclear membrane, which prevents the simultaneous transcription and translation that occurs in prokaryotes. Initiation of protein transcription is started by RNA polymerase. The activity of RNA polymerase is regulated by interaction with regulatory proteins; these proteins can act both positively, as activators, and negatively as repressors. An example of gene regulation in cells is the activity of the trp operon. The trp operon encodes the genes for the synthesis of tryptophan. This type of gene, like the lac operon, is regulated by a repressor that binds to the operator sequences. The activity of the trp repressor is enhanced when it binds tryptophan; in this capacity, tryptophan is known as a corepressor. Since the activity of the trp repressor is enhanced in the presence of tryptophan, the rate of expression of the trp operon is graded in response to the level of tryptophan in the cell. Another example of gene regulation in cells is gene amplification. This is a Technique by which selected DNA from a single cell can be duplicated indefinitely until there is a sufficient amount to analyse by conventional genetic techniques.
Native proteins generally function in a fully folded tertiary structure conformation in biological cells. In contrast, some native proteins have regions which are not properly structured also called as low-complexity domains (LC). For instance, RNA-binding FET family proteins, which include: Fused in sarcoma (FUS), Ewing’s sarcoma (EWS), and TATA-binding protein-associated factor (TAF15) have regions containing low complexity domains characterized by the abundance of only four amino acids; G, S, Q, &Y. FET family proteins are involved in many biological functions such as regulation of transcription, splicing, and mRNA export. Aberrant chromosomal translocations causes LCs of these FET family proteins fused to DNA-binding domains (DBD) of several other proteins which results in over expression of genes causing some types of cancers. Previous studies showed that LCs of FET family proteins activates transcription of genes when fused with DBD, but the mechanism of action of LCs in activating transcription is not known. McKnight et al. tried to unravel the mechanism of action of LCs in activating transcription. They showed that in order to activate transcription, LCs of FET family proteins should polymerize which helps them to bind to C-terminal domain (CTD) of RNA-polymerase II.
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...
Analysis of Transcript - Young Ones Introduction: I have chosen to analyse the beginning of the first episode in the first series of the 80’s TV comedy ‘The Young Ones’. This particular text appeals to me because it is important in how it introduces the characters, as this is the first time the audience ever meet them. Relative Status: Rick and Neil are both students living in the same house; therefore their status should be equal though both are striving for dominance. Rick is defiantly the more dominant of the two, due to his extrovert personality. Both characters are self-centred, for instance, at the beginning of the scene; Neil delivers a monologue where he talks about himself a lot.
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
Progeria causes chromatin perturbations, which result in the formation of DSBs (double-strand breaks) and abnormal DDR (DNA-damage response). Progerin may disrupt DDR pathways in HGPS cells. Progerin accumulation results in disruption of functions of some replication and repair factors, causing the mislocalization of XPA protein to the replication forks, replication fork stalling and, subsequently, DNA DSBs. The binding of XPA to the stalled forks excludes normal binding by repair proteins, leading to DSB accumulation, which actives ATM and ATR checkpoints, and arresting cell-cycle progression.
Precise chromosomal DNA replication during S phase of the cell cycle is a crucial factor in the proper maintenance of the genome from generation to generation. The current “once-per-cell-cycle” model of eukaryotic chromosome duplication describes a highly coordinated process by which temporally regulated replicon clusters are sequentially activated and subsequently united to form two semi-conserved copies of the genome. Replicon clusters, or replication domains, are comprised of individual replication units that are synchronously activated at predetermined points during S phase. Bi-directional replication within each replicon is initiated at periodic AT-rich origins along each chromosome. Origins are not characterized by any specific nucleotide sequence, but rather the spatial arrangement of origin replication complexes (ORCs). Given the duration of the S phase and replication fork rate, adjacent origins must be appropriately spaced to ensure the complete replication of each replicon. Chromatin arrangement by the nuclear matrix may be the underpinning factor responsible for ORC positioning. The six subunit ORC binds to origins of replication in an ATP-dependent manner during late telophase and early G1. In yeast, each replication domain simply contains a single ORC binding site. However, more complex origins are characterized by an initiation zone where DNA synthesis may begin at numerous locations. A single round of DNA synthesis at each activated origin is achieved by “lic...
By utilizing, and, if possible, modifying this special DNA structure, one may see a reduction of age related illness, diseases, and signs of aging. In this review of human telomeres, we will discuss the roles and functions of the telomere, its structure, and the relation of telomere length to aging and tumorigenesis. Role and Functions of The Telomeres Telomeres are special DNA structures that consist of repetitive nucleotide sequences, which serve as a “cap” to protect the ends of the chromosomes. These repetitive sequences can range from thousands of base pairs in Vertebrates to about a few hundreds of base pairs in yeast cells (Oeseburg, et al. 2009). The 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'S Located at the ends of the chromosomes, the telomeres serve as a biological life line for cells.
Mitogen-activated protein (MAP) kinase is a type of catalysis enzyme. Mitogen is a signal that causes cells to undergo mitosis. Since it is a catalysis it will amplify the transduction signal reaction rate across the membrane. MAP kinase cascade involves a series of accessory proteins which then transduces signal from the activated receptor on the cell surface to the regulatory genes in the nucleus. The activated receptor then undergoes phosphorylation. Activated MEK1/2 eventually will activate ERK1/2 which in turn will activate transcription factors of the AP-1 family. The transcription factors now move to the cell nucleus and bind to the AP-1 motif of DNA. The end results activation of transcription a resultant mRNA is transported from nucleus to the
Once histones are modified, the identification of these marks on histones is necessary to understand the relationship between environmental factors and epigenetic changes. Different chemical techniques are used for the purification and separation of histone proteins. To quantify the relative change in a histone modification, it is necessary to measure bands from the blot with the antibody of interest and the control proteins. This utilizes the western blot method, which involves separation by size, transfer to a solid support, and marking target proteins using primary and secondary antibodies. The proteins are separated by molecular weight by gel
Epigenetic is the heritable changes in the gene that does not involve the changes to the sequence of underlying DNA. An epigenetic change is regular and occurs naturally but at the same time it is influenced by factors that include the age of a person, disease state, and lifestyle and also environment the person lives. Epigenetic change can have more damaging effects that may result to such diseases as cancer (Curley, Jensen, Mashoodh & Champagne 2011).The epigenetic change is initiated and sustained by systems like histone modification, non-cordial RNA, and DNA methylation. An epigenetic change is, therefore, causing human disorders as well as fatal diseases. Epigenetic changes live through cell division in cell's life and stays for multiple generations. Early experiences have created foundations of differences in individuals and the manner they interact with the surrounding world. The Epigenetic pathways have integration between nature and nurture during the process of development and the viable changes that persist across generations. Development is a process that involves interaction between nature and nurture. This process, therefore, explains the understanding of gene-environment and it's important in brain development. Brains are refined and have changes in response to experiences before the baby is born. These experiences are first shared between the mother and the fetus where there is a growth sense between what the mother takes in, either by drinking
As previously stated, there are several ways that these changes can occur, but the ones I will be focusing on are changes occurring to methyl and acetyl groups. The mechanism of heritability in animals is information coded into genes. Genes are wrapped around histones in the nucleus. When methyl groups attach to these histones, it winds the genes tighter, and since the shape is altered, it also alters the protein the gene codes for. Generally speaking, when you add a methyl group onto the histones, or "spool" of the gene, it makes it harder to code that gene’s proteins, just like if you got something stuck in the chain on your bike and tried to pedal it. The more methyl groups that build up, the worse the problem becomes. However, in most of the cases acetylation unwinds some of the histones, activating or reactivating a gene. Scientists are explo...
Areas of non-structural DNA, previously known as junk DNA, are now known to be active and able to control gene expression and this is also true of small RNA molecules which act upon messenger RNA by RNA editing (Pinel, 2014). Other mechanisms that regulate gene expression include the widely studied methods of DNA methylation (decreases adjacent gene expression) and histone remodeling (increases or decreases expression) (Pinel, 2014). The final product of genetic expression or regulation can be seen in the example of a caterpillar culminating into a butterfly (Nisic, 2009). They both have the exact DNA, however, the regulation of expression of certain genes during maturation produces the final state of butterfly. As epigenetics continues to examine the process of genetic inheritance and expression, I believe it will transform how we