The Roles of Transcriptional Co-repressors in Plants
Introduction
Transcriptional repression is an important process in many biological pathways. These include development, maintaining homeostasis and regulating physiological processes. In order to control the multitude of pathways, there are a number of repressive mechanisms that are elicited by a diverse set of proteins. These proteins can be broadly classified based on their functional properties. For example, some repressors function at cis-regulatory elements to directly interfere with transcriptional machinery (Fig. 1b). Other repressors alter the chromatin structure surrounding a gene (Fig. 1a), which in turn represses transcription in a less direct fashion. Transcriptional repressors can also be defined by whether they bind DNA directly or bind DNA bound transcription factors to modulate their function (Fig. 1c, d). Proteins that use the later mechanism are termed co-repressors [1]. The Groucho/Tup1 (Gro/Tup1) class is a conserved family of co-repressors found in a range of eukaryotic organisms, established by the metazoan protein Groucho.
Figure 1 - Diversity and classifications of repressors. (a) Repressors can prevent transcription by modifying chromatin. Proteins recruited by the repressor such as histone deacetylase (HDAC), de-novo methyltransferase (Dnmt) and Swi/Snf modify chromatin surrounding a gene to reduce transcription. (b) Repressors prevent gene expression by interfering with transcriptional
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
Also, regulation of proteins occurs at the level of DNA as well as on other levels. In some cells, certain sections of DNA are bundled tight in a mass of proteins, in such a way that no RNA (and thus no protein) can be made from them. This turns off those genes. In other sections, only a few proteins might be keeping the DNA turned off, so that it could quickly be unravelled and used to make proteins.
methyl tag – these are used to either keep genes silent or turn them off. They are added to a cytosine in any sequence of CG sequence of Nucleotides. They can turn off or silence the gene in two ways: (1) by blocking transcription or (2) by recruiting proteins that bind to methylated DNA, which then also block transcription machinery from binding to the active site.
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
When a tumor suppressor gene is effected by a mutation, it loses its control over the cell and the cell does not stop to get inspected. When this happens, the mutation is copied, the cell divides and damage is passed down to the newly formed daughter cells. The mutation then becomes permanent and the now mutated cell will continue to divide and proliferate when it normally would not.
It can turn certain genes on or off by tightly wrapping the structure of the gene making it unreadable and inactive. If it is making a gene active, it simply relaxes the genes structure making them available to read. In further detail, the epigenome alters genetic coding by using the epigenetic tags, or chemical tags, which respond to signals transferred by proteins, ultimately taken to a gene regulatory protein which attaches itself to a certain gene. There are many types of epigenetic tags that make genes effective or not. An example of a tag that turns off genes are Methyl tags. They are attached to a CG base pair, cytosine and guanine, where they block transcription machinery, such as RNA Polymerase, from binding to the DNA. Another way of silencing a gene is by gathering proteins that can bind to DNA with the methyl tags, to then block the transcription machinery. Acetyl tags are an example of tag that turns a gene on. They loosen the Dna from the histone to allow easy access. The acetyl tags are added to lysine, an amino acid, on the tails of histones. Acetyl tgs are just one of the tags that form a histone code, others include methyl, phosphoryl, ubiquitin, SUMO, and
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
Sufu has the ability to bind to GLI1, GLI2 and GLI3 proteins. It is theorized that GLI proteins are binded to Sufu in a head to tail orientation. GL1 is solely found in the nucleus, whereas Sufu can be found expressed in both the nucleus and the cytoplasm. However when they are both expressed together, Sufu brings the GLI1 into the cytoplasm which forces the nucleus to limit its transcription activity. The cytoplasm anchoring model suggests that GLI1 is anchored to the cytoplasm with the help of Sufu. Likewise, Sufu plays a similar role in Drosophilia by halting nuclear processes. Thus, it is found that Sufu travels back and forth between the cytoplasm and nucleus in both Drosophilia and mammals. A second model of Sufu function in mammals suggests the Sufu gene holds the ability of repressing transcription of GLIs. A study found that Sufu restricts GLI transcription by enlisting the help of the mSin3A HDAC corepressor complex. Sufu was also found to increase the ability of GLI1 to bind to DNA. Therefore, simply repressing the Sufu gene is enough to activate GLI transcription, alluding to its key role in the negative regulation of the SHH signaling
Prokaryotic genes are often polycistronic which means that each gene has a start site so each is transcribed independently. However, directly neighboring genes are transcribed in conjunction. Operons are a collection of contiguous genes that code for metabolic enzymes whose transcription is controlled by one operator (Jacob & Monod, 1961). Since operons are coded in one direction, the upstream genes can inhibit the transcription of later genes (Hartl, 2011).
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,
Epigenetics is the study of heritable modifications of your genes being expressed that are not manipulated by mutations in the DNA but by environmental factors. The increasing of inhibiting of transcribing genes is caused by epigenetic changes. The cells in the DNA are packaged together by proteins which are known as histones. DNA is wrapped around the protein (histones). Histone proteins and DNA are tagged chemically which alter gene expression. To impede DNA, DNA methylation is when a methyl group is added consisting of hydrogen and carbon molecules, which are used to limit gene expression. DNA methylation and Histone modification is most commonly known as an epigenetic modification. Epigenetic modifications are a long-term change in, which
The first part of this process is called transcription, where the DNA of a gene is turned into mRNA. The second part of this process, translation, is where the mRNA is turned into a protein. The transcription process is regulated by small proteins called transcription factors. The location of the transcription factors' binding to DNA, determines which genes the cell expresses. Different transcription factors are operating actively in different cell types, which causes different cell types to produce different proteins, which causes each cell to have a unique distinctive
To begin the transcription process, CLOCK and BMAL1 form a heterodimeric transcriptional activator so that three Period genes and two Cryptochrome genes can be transcribed: Per1, Per2, Per3, and Cry1 and Cry2, respectively10, 11. To stop the transcription of the Per and Cry genes, a PER:CRY heterodimer will form and move back to the nucleus and act on CLOCK:BMAL1 to repress transcription of Per and Cry. The regulatory
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
One of the fundamental discoveries of the 20th century was that DNA was the genetic code’s physical structure (Watson & Crick, 1953) and, since then, many studies have disclosed the complicated pattern of regulation and expression of genes, which involve RNA synthesis and its subsequent translation into proteins.