Set1 Case Study

The first major effects of epigenetics on genes can be seen in the role of DNA methylation in mammalian epigenetics. DNA methylation provides a method of gene control in an organism, where it assures proper gene expression, as well as silencing of genes within cells, it does this through the manipulation of chromosome architecture, where it affects the packaging of the DNA by the binding of a methyl group to cytosine (Kullis & Esteller, 2010). The effects of this can

The gene that we are interested in for this project and for the duration of this semester is DMAP1. Not a lot is known about this is a gene, however in other organisms, it is involved in the methylation of DNA. DMAP1 is responsible for encoding a protein that associates with another protein that methylates DNA. The methylation of DNA alters the DNA structure and makes it unavailable to transcription factors, so the mutation of DMAP1 could lead to changes in transcription and gene regulation. For example, if DMAP1 were mutated, less DNA methylation might occur and more areas of DNA could be accessible to transcription factors and ‘active’, making more genes transcribed than should be. Gene alterations are important as they can lead

The study greatly helped in understanding the mechanism of nutrition and epigenetic inheritance to the child while in the womb. It has been shown through animal studies that a methyl rich diet of the mother gives a progeny with a highly methylated DNA. Specifically, studies in mice have shown that diet affects the Agouti gene (present in all mammals) when the gene is not methylated the mice shows a yellow coat, a fatter complexion and is likely to develop diabetes and cancer. Unlike the healthy mice

To understand epigenetics and transgenerational epigenetics in greater detail we need to obtain a clearer picture of the underlying molecular mechanisms. Lim and Brunet (2013) revealed that environmental stimuli can influence the chromatin structure by noncoding RNAs- including siRNA (small interfering RNA, worm), piRNA ((Piwi-interacting RNA, worm and fly), viRNA (small interfering RNAs derived from virus, worm), miRNA (micro RNA, mice)- DNA methylation (mice, rat) and histone modification (with the help of Histone methyltransferase poteins)- H3K4me2/3 (worm), H3K36me3 (worm), H3K36me3 (worm, fly), H3K9me2/3 (worm, fly), H3K27me3 (mice, human). Prion proteins might also play role (yeast). These changes might influence the metabolics, which changes the expression of different chemicals and are themselves potential environmental stress factors; thus, they could initiate epigenomic changes. Chromatin modifications

Methylation is the process where methyl groups are attached to the sequence of DNA code letter and to the histone groups that the DNA encircle; whereas, acetylation is the process where acetyl groups are attached to the histone tails. The methylation decreases gene expression while the acetylation increases gene expression. Epigenetic inheritance mentions in the article supports the content that we cover in class, in which epigenetic inheritance means modification to DNA other than sequence that can be altered by environment or diet and can be passed on to next

During methylation, methyl groups (CH3) are attached to histone tails with the aid of histone methyltransferases (HMTs). These proteins transfer one, two, or three methyl groups from S-adenosyl-L-methionine to lysine or arginine residues. Lysine methylation involves a lysine methyltransferase that specifically targets and methylates lysine within the N-terminal tails. Similarly, arginine methylation occurs through the transfer of methyl groups from SAM to the ɯ-guanidino group of arginine. Although histone methylation does not change the charge of residues and does not greatly impact nucleosome interactions for chromatin folding, it results in binding sites for certain enzymes, which enables the regulation of chromatin condensation and nucleosome mobility. Methylation can also block the binding of proteins that interact with unmethylated histones and inhibit other modifications. Therefore, histone methylation regulates genes by promoting the binding of positive transcription factors and by blocking the attachment of negative transcription factors. However, some methylations can prevent gene transcription by mediating heterochromatin formation. For example, H3-K9 and H3-K27 methylation silences gene expression at certain euchromatic

Epigenetic modifications to the human genome have increasingly become the subject of scientific research due to a presumptive role in the pathology and progression of degenerative diseases. Conventionally, methylation of a nucleotide residue is associated with gene repression, whereas acetylation of a nucleotide residue is associated with gene expression. Through a member of the DNA methyltransferase protein family, the formation of 5-methylcytosine (5mC) from a previously unmodified cytosine residue is a classic representation of a widely-occurring, principal epigenetic modification event. This process is subject to dynamic regulation and as such, the regulatory mechanisms have yet to be elucidated. In regards to demethylation of these particular residues, humans lack a corresponding methylcytosine specific DNA glycosylase; however, a potential alternate pathway has been identified. Catalyzed by the human ten eleven translocation 1 (TET1) proteins, oxidation of 5mC results in formation of 5-hydroxymethylcytosine (5hmC); when 5hmC is further subject to oxidation, 5-formylcytosine (5fC) is produced. These oxidized derivatives are suspected to be substrates designated for removal by the base excision repair pathway.

Chromatin changes have been linked with all phases of tumour creation and development. The best categorized are epigenetically mediated transcriptional-silencing activities that are related by increases in DNA methylation, specifically at promoter regions of genes that control important cell functions. Current proof shows that epigenetic changes would possibly 'addict' cancer cells to alter signal-transduction pathways in the early stages of tumors development. Reliance on these pathways for cell proliferation or existence allows them to obtain genetic mutations in the same pathways, providing the cell with careful advantage that promote tumors progression. Approaches to inverse epigenetic gene silencing might consequently be beneficial in cancer prevention and treatment [75].

DNA is associated with specific proteins called histones which compact and package the chromosomes into the nucleus. The resulting DNA-protein complex is called chromatin. The packaging of DNA into chromatin can impact the ability of the numerous proteins and enzymes to gain access to specific genes before activating their transcription. The chromatin structure can be altered, either being loosened to facilitate gene expression or tightened to limit gene expression. These alternations are largely mediated by reversible modifications of the histones through a dynamic, tightly regulated process called chromatin remodeling. Chromatin remodeling mediates differential gene expression and is therefore crucial for development, cell type-specific gene

Epigenetic mechanisms such as DNA methylation and histone modifications are widely considered to be important in controlling the differentiation of cells. However some argue that since these mechanisms are not seen or transient in model organisms such as worms and flies that epigenetics cannot be important. However it is also important to mention that there are very different definitions of the word epigenetics formed from independent reasoning which may affect the debate on whether epigenetics is important or not in controlling cell differentiation. (Berger et al., 2009)For example, to Conrad Waddington, it was the study of epigenesist ie. How genotypes give rise to phenotypes during development. On the other hand, Arthur Riggs

Epigenetics represents a complex layer onside DNA sequence reflecting the environmental factors. It studies the changes in organisms lead to gene expression level change but the genetic code stay the same. Epigenetics factors play an important role in regulating gene expression. There are two main components of the epigenetic code, DNA methylation and histone modification. Epigenetics changes are common in different areas, across different species. For human, epigenetics is extremely important on complex disease or disorder studies.

MutSα, one of the many components of human MMR, is known to affect all of the aforementioned processes. In instances where epigenetic silencing or mutations of genes that code for the proteins of MutSα occur, DNA mismatches are allowed to persist, which collectively increase the probability that microsatellite instabilities (a mutator phenotype) occur. Microsatellites are known to cause an increased tolerance to DNA methylation, hyperrecombination, and numerous other perturbations on DNA that can eventually lead to cancers and/or defective progeny.3, 11 Considering the importance of MMR to human health, a thorough understanding of the structure, function, and temporal relationships between the many components of MMR is

Epigenetic processes intimately link environmental factors to our genetic code, by allowing outside events to leave biochemical footprints on our genome. Modern epigenetics can be defined as ‘the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states' (Bird, 2007) (see Box 1 for a detailed definition of epigenetics). Therefore, epigenetics offers mechanisms by which cells that are equipped with identical genetic information can acquire and maintain an individual molecular fingerprint reflecting not only the cell's history, but also programming its response to future events (Levenson and Sweatt, 2006). Two of the most prominent epigenetic mechanisms are DNA methylation (DNAme) and histone

The FACT complex is a highly conserved general histone chaperone protein that is essential for transcription and DNA replication (Abe et al., 2011; Belotserkovskaya and Reinberg, 2004; Orphanides et al., 1998). The complex has also been shown to play important roles in DNA damage responses, centromere deposition, recombination and DNA methylation (Ikeda et al., 2011; Kumari et al., 2009; Okada et al., 2009; Oliveira et al., 2014). The FACT complex is thought to destabilize

Zfp322a may contribute to chromatin remodeling associated with maintenance of mES chromatin. Ma et al. 2014 identified a large number of genes enriched with Zfp322a that were involved in chromatin modification,