Histone Protein

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 EZH2 (enhance of zeste homolog2) is an enzyme that in humans is fixed by EZH2 and its supply the information’s about making of enzyme called a histone me-thyltransferase. The ploycomb group (PcG) is a protein with the catalytic subunit of the PRC2 (polycomb repressive complex) which the transcriptional involved in maintaining the repressive of genes cells and also the EZH2 mainly performs as a silence gene. The EZH2 performs the role by addition of methyl groups on the ly-sine 27 of histone H3, a modification leading chromatin

It has been suggested that abnormalities in the activity or expression of HDACs can lead to an imbalance of HDAC relative to histone acetyltransferase activity resulting in diminished expression of regulatory genes, which control the cell cycle and apoptosis developing tumorigenesis (Licciardi, Ververis, Hiong & Karagiannis, 2013). In some cases, HDAC enzymes are abnormally recruited to gene promoters, which constitutively repress gene expression causing cancer. In addition, HDACs alter gene expression due to the posttranslational deacetylation modification of various nonhistone protein substrates, such as DNA-binding proteins, DNA-repair proteins, transcription factors, signal-transduction molecules, and chaperone proteins(Licciardi, Ververis, Hiong & Karagiannis,

CAF1 and anti-silencing Function 1 (ASF1) together interact with helicase to moves the old H3-H4’s to a new strand. So if CAF1 does not interact with ASF1, the H3-H4’s would not be moved to the new strand. The nucleosome can’t be formed correctly without the histones in the correct place. Liu and researchers found that Asf1 and CAF-1 interact directly through CAF-1 subunit, Cac2’s B domain. This

One of the main conclusions drawn from this experiment was that the cis memory system is the one used to inherit modified histones because they concluded that epigenetic memory is stored locally in FLC gene. One of the main pieces of evidence to support this is in Figure 3 of this paper. This figure describes heritable expression states, and it is concluded that the cis memory system is used because mitotic stability of all four possible combinations (ON/ON, ON/OFF, OFF/ON, and OFF/OFF) are observed. ‘Mixed’ ON/OFF and OFF/ON states are only seen in cis systems, thus the trans system cannot be implemented. Using this they were also able to show that two identical DNA sequences can have different transcriptional states in the same nucleus, which is only demonstrated by cis memory. Another conclusion they were able to make was that PRC2 is necessary for histone

Histones are the basic proteins that wrap DNA into nucleosomes. Each histone has a flexible N-terminal tail, which carry the sites for modification. Histones fall into five protein families, the core histones H2A, H2B, H3 and H4, and the linker histone family H1.

To capture important components of nucleosome formation, such as the propensity of nucleosomes not to form for A-tract sequences. There have been recent attempts to model DNA with empirical force fields such as CHARMM and AMBER, but the computational complexity associated with modeling nucleosome structures has so-far restricted these simulations to short segments (18 bp) with specific histone-DNA interactions have been ignored. This study will merge different computational approaches to resolve results obtained through experimental studies which ultimately should be linked, forming a consistent theory;

A seemingly novel gene sequence has been discovered in fruit flies from Nicholas Harden’s lab at Simon Fraser University using random PCR primers. Attempts at purifying and characterizing this gene have been elusive. Here, we show methods for isolating, amplifying, and purifying the gene of interest for analysis. Using polymerase chain reaction to amplify the gene, it is then ligated into a pGEM-T Easy vector for TA cloning experiments. Transformation for further vector proliferation is done on competent Escherichia coli cells. Subsequently, the vector is purified through plasmid preparation and sent to an off-site location for sequencing. Upon sequence analysis, it is suggested that the gene of interest, will die slowly, belongs to the WD repeat WDR5/wds family, and has implications in histone acetyltransferase activity.

Scientists have known for several decades that cancer may be caused by mutations in the DNA of cells. These mutations may result from exposure to certain substances (e.g. radiation, benzene) or they may occur spontaneously in the process of cell division, especially in the context of aging. Recently, researchers have discovered another level of inherited cellular information separate from the genes themselves. Epigenetics is the study of modifications to genes that change their patterns of expression. Epigenetic processes can silence a gene or even an entire chromosome. They can cause normally silent genes to be expressed, and can change the process of transcription so that the nucleotides are transcribed in a different order. Normally, epigenetic information is stabilized early in development and is maintained as cells divide. However, over time, mutations or epigenetic drift may change the inherited pattern. This type of event often results in disease such as cancer (Jones & Baylin 2002).

In bacteria and in eukaryotes, the continuing presence of the activator is required to keep the gene on. Scientists argue that active genes often associated with acetylated nucleosomes not because of epigenetic reasons but because of other reasons. One reason is that as genes are transcribed, their nucleosomes are removed and then replaced to make way for RNA polymerase which is involved in transcription. They argue that this nucleosome-replacement machinery works to replace one set of nucleosomes with others that are more highly acetylated. Therefore, nucleosome acetylation accompanies but does not cause transcription. (Ptashne, 2013)

The first stage is chromatin modification. Usually, genes within heterochromatin are not expressed since it is so compact and dense. Chemical modifications to histones influence whether the chromatin is condense or not. For example, histone acetylation promotes transcription by opening up the chromatin structure. In contrast, DNA methylation reduces transcription by the addition of methyl groups, leading to condensation. Individual genes as well as long segments of the DNA can be heavily methylated in cells, preventing them from being expressed. Methylation patters can be inherited however, unlike mutations, they can be reversed.

It combines information on both proteins and DNA and how the two are connected to one another. This article explains the significance of protein function and variety due to its ability to affect other parts of the cell that are critical for life. Both Chapter 3 and Chapter 4 are connected with this chapter because we learned about how structure determines the multiple different functions of proteins as well as DNA structure and how DNA can shorten or be altered due to mutations which will affect the

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.

It is a powerful tool in regulating the differential expression of genome in different tissues of the same organisms. Mechanisms of chromatin remodeling and post-translational modifications of biomolecules play an important role in regulating expression of particular set of genes in particular tissues (Bryan, 2001). Role of posttranslational modifications such as acetylation, phosphorylation and methylation etc determining in any peculiar phenotype is well documented; and impairment of these modifications (epi-mutations) may result in number of diseases. Thus, epigenetic regulation necessitates reconsidering the definition of phenotype, and it is already known that a particular cellular phenotype is not solely defined by the DNA sequence present in the

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