Transcription regulation plays an essential role in the development, complexity, and homeostasis of all organisms, as transcription is the first step in the universal pipeline of biological information flow from genome to proteome.
What is transcriptional regulation?
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription ), thereby orchestrating gene activity.
What is the function of transcription factors?
Transcription factors. Transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a given gene. The power of transcription factors resides in their ability to activate and/or repress wide repertoires of downstream target genes.
What is the role of repressors in transcription regulation?
The regulation of transcriptionby repressors as well as by activators considerably extends the range of mechanisms that control the expression of eukaryotic genes. One important role of repressors may be to inhibit the expression of tissue-specific genes in inappropriate cell types.
What is gene regulation and why is it important?
Gene regulation is how a cell controls which genes, out of the many genes in its genome, are “turned on” (expressed). Thanks to gene regulation, each cell type in your body has a different set of active genes—despite the fact that almost all the cells of your body contain the exact same DNA.
What is the benefit of regulation of gene at transcription?
A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response.
Why is it important to regulate transcription and translation in living organisms?
Regulation of the two main steps of protein production — transcription and translation — is critical to this adaptability. Cells can control which genes get transcribed and which transcripts get translated; further, they can biochemically process transcripts and proteins in order to affect their activity.
Why are transcription factors so important?
Transcription factors are vital molecules in the control of gene expression, directly controling when, where and the degree to which genes are expressed. They bind to specific sequences of DNA and control the transcription of DNA into mRNA.
Why are transcriptional regulator proteins necessary?
Why are transcriptional regulator proteins necessary? The basal transcription apparatus can only produce minimal levels of transcription without them. The basal transcription apparatus will repress transcription without them. The transcriptional regulator proteins keep the apparatus from being degraded by enzymes.
What happens if gene expression is not regulated?
The control of gene expression is extremely complex. Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer.
What is involved in regulation of transcription?
First, transcription is controlled by limiting the amount of mRNA that is produced from a particular gene. The second level of control is through post-transcriptional events that regulate the translation of mRNA into proteins. Even after a protein is made, post-translational modifications can affect its activity.
Are transcription factors always needed?
Transcription factors are essential for the regulation of gene expression and are, as a consequence, found in all living organisms. The number of transcription factors found within an organism increases with genome size, and larger genomes tend to have more transcription factors per gene.
Why is transcription and translation important?
Both transcription and translation are equally important in the process of genetic information flow within a cell, from genes in DNA to proteins. Neither process can occur without the other.
What is the role of transcription factors in transcription quizlet?
What is the role of transcription factors? Transcription factors are required for RNA pol II binding to promoter. TFs are DNA binding proteins, but can also bind other TFs. They assist in bringing RNA pol II in close proximity of the promoter.
Why is transcriptional silencing important?
Transcriptional gene silencing Gene silencing is important for development, stress responses, and suppression of viruses, transposons, and transgenes [19–23]. Several epigenetic phenomena such as genome imprinting [24, 25] and X chromosome inactivation [26, 27] are caused by transcriptional gene silencing (TGS).
Why is transcription and translation important?
Both transcription and translation are equally important in the process of genetic information flow within a cell, from genes in DNA to proteins. Neither process can occur without the other.
Why are transcription and translation so important to the cell?
The purpose of transcription is to make RNA copies of individual genes that the cell can use in the biochemistry. The purpose of translation is to synthesize proteins, which are used for millions of cellular functions.
Why is transcription and translation important for cells?
In order for a cell to manufacture these proteins, specific genes within its DNA must first be transcribed into molecules of mRNA; then, these transcripts must be translated into chains of amino acids, which later fold into fully functional proteins.
What is the importance of translation and transcription in the maintenance of normal functioning within the cell?
Transcription and translation are processes a cell uses to make all proteins the body needs to function from information stored in the sequence of bases in DNA.
What is transcriptional regulation?
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription ), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control ...
How do transcription factors work?
Transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a given gene. There are approximately 1,400 transcription factors in the human genome and they constitute about 6% of all human protein coding genes. The power of transcription factors resides in their ability to activate and/or repress wide repertoires of downstream target genes. The fact that these transcription factors work in a combinatorial fashion means that only a small subset of an organism's genome encodes transcription factors. Transcription factors function through a wide variety of mechanisms. In one mechanism, CpG methylation influences binding of most transcription factors to DNA—in some cases negatively and in others positively. In addition, often they are at the end of a signal transduction pathway that functions to change something about the factor, like its subcellular localization or its activity. Post-translational modifications to transcription factors located in the cytosol can cause them to translocate to the nucleus where they can interact with their corresponding enhancers. Other transcription factors are already in the nucleus, and are modified to enable the interaction with partner transcription factors. Some post-translational modifications known to regulate the functional state of transcription factors are phosphorylation, acetylation, SUMOylation and ubiquitylation . Transcription factors can be divided in two main categories: activators and repressors. While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions. It may also happen that a repressor may function by allosteric competition against a determined activator to repress gene expression: overlapping DNA-binding motifs for both activators and repressors induce a physical competition to occupy the site of binding. If the repressor has a higher affinity for its motif than the activator, transcription would be effectively blocked in the presence of the repressor. Tight regulatory control is achieved by the highly dynamic nature of transcription factors. Again, many different mechanisms exist to control whether a transcription factor is active. These mechanisms include control over protein localization or control over whether the protein can bind DNA. An example of this is the protein HSF1, which remains bound to Hsp70 in the cytosol and is only translocated into the nucleus upon cellular stress such as heat shock. Thus the genes under the control of this transcription factor will remain untranscribed unless the cell is subjected to stress.
What is the function of enhancers in transcription?
Enhance function in regulation of transcription in mammals. An active enhancer regulatory sequence of DNA is enabled to interact with the promoter DNA regulatory sequence of its target gene by formation of a chromosome loop.
How are transcriptional initiation and termination mediated?
Transcriptional initiation, termination and regulation are mediated by “DNA looping” which brings together promoters, enhancers, transcription factors and RNA processing factors to accurately regulate gene expression. Chromosome conformation capture (3C) and more recently Hi-C techniques provided evidence that active chromatin regions are “compacted” in nuclear domains or bodies where transcriptional regulation is enhanced. The configuration of the genome is essential for enhancer-promoter proximity. Cell-fate decisions are mediated upon highly dynamic genomic reorganizations at interphase to modularly switch on or off entire gene regulatory networks through short to long range chromatin rearrangements. Related studies demonstrate that metazoan genomes are partitioned in structural and functional units around a megabase long called Topological association domains (TADs) containing dozens of genes regulated by hundreds of enhancers distributed within large genomic regions containing only non-coding sequences. The function of TADs is to regroup enhancers and promoters interacting together within a single large functional domain instead of having them spread in different TADs. However, studies of mouse development point out that two adjacent TADs may regulate the same gene cluster. The most relevant study on limb evolution shows that the TAD at the 5’ of the HoxD gene cluster in tetrapod genomes drives its expression in the distal limb bud embryos, giving rise to the hand, while the one located at 3’ side does it in the proximal limb bud, giving rise to the arm. Still, it is not known whether TADs are an adaptive strategy to enhance regulatory interactions or an effect of the constrains on these same interactions. TAD boundaries are often composed by housekeeping genes, tRNAs, other highly expressed sequences and Short Interspersed Elements (SINE). While these genes may take advantage of their border position to be ubiquitously expressed, they are not directly linked with TAD edge formation. The specific molecules identified at boundaries of TADs are called insulators or architectural proteins because they not only block enhancer leaky expression but also ensure an accurate compartmentalization of cis-regulatory inputs to the targeted promoter. These insulators are DNA-binding proteins like CTCF and TFIIIC that help recruiting structural partners such as cohesins and condensins. The localization and binding of architectural proteins to their corresponding binding sites is regulated by post-translational modifications. DNA binding motifs recognized by architectural proteins are either of high occupancy and at around a megabase of each other or of low occupancy and inside TADs. High occupancy sites are usually conserved and static while intra-TADs sites are dynamic according to the state of the cell therefore TADs themselves are compartmentalized in subdomains that can be called subTADs from few kb up to a TAD long (19). When architectural binding sites are at less than 100 kb from each other, Mediator proteins are the architectural proteins cooperate with cohesin. For subTADs larger than 100 kb and TAD boundaries, CTCF is the typical insulator found to interact with cohesion.
What are enhancers in DNA?
Enhancers or cis-regulatory modules/elements (CRM/CRE) are non-coding DNA sequences containing multiple activator and repressor binding sites. Enhancers range from 200 bp to 1 kb in length and can be either proximal, 5’ upstream to the promoter or within the first intron of the regulated gene, or distal, in introns of neighboring genes or intergenic regions far away from the locus. Through DNA looping, active enhancers contact the promoter dependently of the core DNA binding motif promoter specificity. Promoter-enhancer dichotomy provides the basis for the functional interaction between transcription factors and transcriptional core machinery to trigger RNA Pol II escape from the promoter. Whereas one could think that there is a 1:1 enhancer-promoter ratio, studies of the human genome predict that an active promoter interacts with 4 to 5 enhancers. Similarly, enhancers can regulate more than one gene without linkage restriction and are said to “skip” neighboring genes to regulate more distant ones. Even though infrequent, transcriptional regulation can involve elements located in a chromosome different to one where the promoter resides. Proximal enhancers or promoters of neighboring genes can serve as platforms to recruit more distal elements.
How does up regulation of genes in mammals work?
Up-regulated expression of genes in mammals can be initiated when signals are transmitted to the promoters associated with the genes. Cis-regulatory DNA sequences that are located in DNA regions distant from the promoters of genes can have very large effects on gene expression, with some genes undergoing up to 100-fold increased expression due to such a cis-regulatory sequence. These cis-regulatory sequences include enhancers, silencers, insulators and tethering elements. Among this constellation of sequences, enhancers and their associated transcription factor proteins have a leading role in the regulation of gene expression.
How is DNA compacted?
In eukaryotes, genomic DNA is highly compacted in order to be able to fit it into the nucleus. This is accomplished by winding the DNA around protein octamers called histones, which has consequences for the physical accessibility of parts of the genome at any given time. Significant portions are silenced through histone modifications, and thus are inaccessible to the polymerases or their cofactors. The highest level of transcription regulation occurs through the rearrangement of histones in order to expose or sequester genes, because these processes have the ability to render entire regions of a chromosome inaccessible such as what occurs in imprinting.
What is the role of transcription regulation?
Transcription regulation plays an essential role in the development, complexity, and homeostasis of all organisms , as transcription is the first step in the universal pipeline of biological information flow from genome to proteome.
How does transcription regulation occur?
Transcription regulation of many genes occurs via DNA looping, which brings into close proximity proteins bound at distant sites along the double helix. Looping produces shortening of the DNA molecule and activation or repression (depending on the gene and proteins involved) of promoters adjacent or within the loop region.
How does DNA regulation affect transcription?
Cellular functions including transcription regulation, DNA repair, and DNA replication need to be tightly regulated. DNA sequence can contribute to the regulation of these mechanisms. This is examplified by the consensus sequences that allow the binding of specific transcription factors, thus regulating transcription rates. Another layer of regulation resides in modifications that do not affect the DNA sequence itself but still results in the modification of chromatin structure and properties, thus affecting the readout of the underlying DNA sequence. These modifications are dubbed as “epigenetic modifications” and include, among others, histone modifications, DNA methylation, and small RNAs. While these events can independently regulate cellular mechanisms, recent studies indicate that joint activities of different epigenetic modifications could result in a common outcome. In this chapter, I will attempt to recapitulate the best known examples of collaborative activities between epigenetic modifications. I will emphasize mostly on the effect of crosstalks between epigenetic modifications on transcription regulation, simply because it is the most exposed and studied aspect of epigenetic interactions. I will also summarize the effect of epigenetic interactions on DNA damage response and DNA repair. The involvement of epigenetic crosstalks in cancer formation, progression, and treatment will be emphasized throughout the manuscript. Due to space restrictions, additional aspects involving histone replacements [Park, Y. J., and Luger, K. (2008). Histone chaperones in nucleosome eviction and histone exchange. Curr. Opin. Struct. Biol.18, 282–289.], histone variants [Boulard, M., Bouvet, P., Kundu, T. K., and Dimitrov, S. (2007). Histone variant nucleosomes: Structure, function and implication in disease. Subcell. Biochem. 41, 71–89; Talbert, P. B., and Henikoff, S. (2010). Histone variants—Ancient wrap artists of the epigenome. Nat. Rev. Mol. Cell Biol.11, 264–275.], and histone modification readers [de la Cruz, X., Lois, S., Sanchez-Molina, S., and Martinez-Balbas, M. A. (2005). Do protein motifs read the histone code? Bioessays27, 164–175; Grewal, S. I., and Jia, S. (2007). Heterochromatin revisited. Nat. Rev. Genet.8, 35–46.] will not be addressed in depth in this chapter, and the reader is referred to the reviews cited here.
How does DNA methylation regulate gene expression?
DNA methylation is an epigenetic mechanism that occurs by adding a methyl (CH3) group to the 5-carbon on the cytosine base after DNA is synthesized , thereby controlling gene expression. Transgenes can be turned off by DNA methylation if they “behave in a bad manner” ( Zheng et al., 2016 ). Given that DNA and histones are integral components of chromatin, DNA methylation and histone modifications often coordinate with each other to compose a complex epigenetic regulatory network.
What is epigenetic therapy?
Some investigators have considered epigenetic phenomenon as a bridge between genotype and phenotype ( Bernstein, Meissner, & Lander, 2007; Reik, 2007 ). In recent years, “epigenetic therapy” has emerged as a new therapeutic target to combat gene “silencing” to achieve activation of beneficial genes.
Why do we need time filtering for dynamic changes?
Due to the Brownian diffusion of the particle and the overlap between the looped and unlooped distributions , the determination of the dynamic changes usually requires time filtering of the raw data, significantly impacting the measurement time resolution and the reliability of the determination of the kinetic constants. Methods have been proposed to either correct for such a drawback ( Colquhoun and Sigworth, 1983; van den Broek et al., 2006; Vanzi et al., 2006) or determine the kinetic constants from the raw data ( Beausang et al., 2007a,c; Qin et al., 2000 ). Nevertheless, these approaches require the knowledge of the kinetic mechanism of the reaction being considered and their application is limited to fairly simple reaction schemes.
What is the looping mechanism of DNA?
Figure 9.1. Schematic representation of the looping mechanism. Proteins bound at distant sites along the DNA can interact establishing a DNA loop. The loop shortens the DNA, reducing the range of diffusion of the tethered bead.
Why do transcription factors loop?
DNA looping. Transcription factors bound at distant enhancers are able to interact with general transcription factors at the promoter because the intervening DNA can form loops. There is therefore no fundamental difference between the action of transcription (more...)
What is binding of a repressornear the transcription start site?
For example, the binding of a repressornear the transcription start site can block the interaction of RNA polymeraseor general transcription factorswith the promoter, which is similar to the action of repressors in bacteria. Other repressors compete with activators for binding to specific regulatory sequences.
How are genes controlled in eukaryotes?
The expression of eukaryotic genes is controlled primarily at the level of initiation of transcription, although in some cases transcription may be attenuated and regulated at subsequent steps. As in bacteria, transcription in eukaryotic cells is controlled by proteins that bind to specific regulatory sequences and modulate the activity of RNA polymerase. The intricate task of regulating gene expression in the many differentiated cell types of multicellular organisms is accomplished primarily by the combined actions of multiple different transcriptional regulatory proteins. In addition, the packaging of DNA into chromatin and its modification by methylation impart further levels of complexity to the control of eukaryotic gene expression.
What are cis-acting regulatory sequences?
cis-Acting Regulatory Sequences: Promoters and Enhancers. As already discussed, transcriptionin bacteria is regulated by the binding of proteinsto cis-acting sequences (e.g., the lacoperator) that control the transcription of adjacent genes. Similar cis-acting sequences regulate the expression of eukaryotic genes.
Which sequences are binding sites for transcription factors?
Other cis-acting sequences serve as binding sites for a wide variety of regulatory factors that control the expression of individual genes.
Does methylation inhibit transcription?
Methylation inhibits transcription of these genes via the action of a protein, MeCP2, that specifically binds to methylated DNA and represses transcription. Interestingly, MeCP2 functions as a complex with histone deacetylase, linking DNA methylation to alterations in histone acetylation and nucleosomestructure.
Does decondensation of chromatin make DNA accessible?
Decondensation of chromatin, however, is not sufficient to make the DNAan accessible template for transcription. Even in decondensed chromatin, actively transcribed genes remain bound to histonesand packaged in nucleosomes, so transcription factors and RNA polymeraseare still faced with the problem of interacting with chromatin rather than with naked DNA. The tight winding of DNA around the nucleosomecore particle is a major obstacle to transcription, affecting both the ability of transcription factors to bind DNA and the ability of RNA polymerase to transcribe through a chromatin template. This inhibitory effect of nucleosomes is relieved by acetylation of histones and by the binding of two nonhistone chromosomal proteins(called HMG-14and HMG-17) to nucleosomes of actively transcribed genes. (HMG stands for high-mobility group proteins; these proteins migrate rapidly during gel electrophoresis.) Additional proteins called nucleosome remodeling factorsfacilitate the binding of transcription factors to chromatin by altering nucleosome structure.
What is gene transcription control?
Gene transcription rate-controlling is known as transcriptional regulation hindering or helping the binding of RNA polymerase to DNA. The transcription control of genetics and molecular biology is how cells regulate the transcription of DNA in RNA and regulate genetic function. transcription. In different ways, a single gene can be controlled from changing the number of RNA copies to briefly regulating the transcription of the gene.
Why is translation regulation important?
The translation regulation applies to the protein synthesized by mRNA. This regulation is important for cellular stress response, differentiation, and development. This regulation is essential as it contributes to much quicker cellular adaptation by controlling the protein concentration directly compared with transcription regulation.
What is translation regulation?
Translation regulation refers to protein synthesized from its mRNA level regulations. Gene transcription rate-controlling is known as transcriptional regulation hindering or helping the binding of RNA polymerase to DNA.
Which eukaryotic elongation factor regulates the polypeptide chain from site A- site to?
GTP-dependent translocase is the eukaryotic elongation factor 2 (eEF2) that regulates the polypeptide chain from site A- site to site P- site on ribosomes. Phosphorylation of threonine 56 inhibits the binding of eEF2 to ribosomes. It has been shown that cellular stressors such as anoxia cause translation inhibition through these biochemical interactions.
What is the initiation factor of translation?
The initiation of the translation relies on the ribosomes for the sequence Shine-Dalgarno. Initiation is also regulated by proteins known as initiation factors that provide kinetic support for binding the 3'-UAC-5' anticodon between the initiation codon and met-tRNA.
What is elongation of RNA?
RNA transcript elongation: When the promoter binds polymerase, various other factors are necessary to exit the promoter and initiate successful RNA transcriptions.
Which elements of DNA bind with proteins and RNA polymerase for successful transcription initiation gene upstream directly?
Elements of DNA that bind with proteins and RNA polymerase for successful transcription initiation gene upstream directly are known as promoters.
How does gene regulation work?
Gene regulation is how a cell controls which genes, out of the many genes in its genome, are “turned on” (expressed). Thanks to gene regulation, each cell type in your body has a different set of active genes—despite the fact that almost all the cells of your body contain the exact same DNA. These different patterns of gene expression cause your various cell types to have different sets of proteins, making each cell type uniquely specialized to do its job.
Why is it important to regulate gene expression?
The regulation of gene expression conserves energy and space.
What is the process of turning on a gene to produce RNA and protein called?
The process of turning on a gene to produce RNA and protein is called gene expression. Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed.
What is growth factor signaling?
Growth factor signaling is complex and involves the activation of a variety of targets, including both transcription factors and non-transcription factor proteins.
How do cells regulate the synthesis of proteins?
All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and protein is called gene expression. Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed.
Where is gene expression controlled in prokaryotic cells?
Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level. Eukaryotic cells, in contrast, have intracellular organelles that add to their complexity. In eukaryotic cells, the DNA is contained inside the cell’s nucleus and there it is transcribed into RNA.
Why is gene expression energy efficient?
The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required.
