Instruct: Given a question, retrieve documents that can help answer the question.
Query: What triggers transcription in DNA?
RNA polymerase, together with one or more general transcription factors, binds to promoter DNA. RNA polymerase creates a transcription bubble, which separates the two strands of the DNA helix. This is done by breaking the hydrogen bonds between complementary DNA nucleotides. RNA polymerase adds RNA nucleotides (which are complementary to the nucleotides of one DNA strand). RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand. Hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand. If the cell has a nucleus, the RNA may be further processed. This may include polyadenylation, capping, and splicing. The RNA may remain in the nucleus or exit to the cytoplasm through the nuclear pore complex.
During latency, most of the Herpes DNA is inactive, with the exception of LAT, which accumulates within infected cells.
The region of HHV DNA which encodes LAT is known as LAT-DNA. After splicing, LAT is a 2.0-kilobase transcript (or intron) produced from the 8.3-kb LAT-DNA. The DNA region containing LAT-DNA is known as the "Latency Associated Transcript Region".
cGAS is found in the cytosol and is responsible for detecting cytosolic double stranded DNA, normally found in the cell nucleus, in order to stimulate production of IFN-β. Upon directly binding cytosolic DNA, cGAS forms dimers to catalyze production of 2’3’-cGAMP from ATP and GTP. cGAMP then acts a second messenger, binding to STING, to trigger activation of the transcription factor IRF3. IRF3 leads to transcription of type-1 IFN-β. cGAS is unable to produce 2’3’-cGAMP in the presence of RNA.
Z-DNA is commonly believed to provide torsional strain relief during transcription, and it is associated with negative supercoiling. However, while supercoiling is associated with both DNA transcription and replication, Z-DNA formation is primarily linked to the rate of transcription.
Outside of the essential processes of replication or transcription, DNA must be kept as compact as possible, and these three states help this cause. However, when transcription or replication occurs, DNA must be free, and these states seriously hinder the processes. In addition, during replication, the newly replicated duplex of DNA and the original duplex of DNA become intertwined and must be completely separated in order to ensure genomic integrity as a cell divides. As a transcription bubble proceeds, DNA ahead of the transcription fork becomes overwound, or positively supercoiled, while DNA behind the transcription bubble becomes underwound, or negatively supercoiled. As replication occurs, DNA ahead of the replication bubble becomes positively supercoiled, while DNA behind the replication fork becomes entangled forming precatenanes. One of the most essential topological problems occurs at the very end of replication, when daughter chromosomes must be fully disentangled before mitosis occurs. Topoisomerase IIA plays an essential role in resolving these topological problems.
Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Also, transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read. Unfortunately, these interactions are very difficult to study because biological molecules morph shapes so easily. In 2008 it was noted that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself effects how the molecule responds to supercoiling. For example, the researchers identified a specific sequence of DNA that regulates transcription speed; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA. It is hypothesized that these structural changes might trigger stress elsewhere along its length, which in turn might provide trigger points for replication or gene expression. This implies that it is a very dynamic process in which both DNA and proteins each influences how the other acts and reacts.
In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized transcript RNA that trigger processes which release the transcript RNA from the transcriptional complex. These processes include the direct interaction of the mRNA secondary structure with the complex and/or the indirect activities of recruited termination factors. Release of the transcriptional complex frees RNA polymerase and related transcriptional machinery to begin transcription of new mRNAs.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [e.g., thyroid hormone receptor-(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize.
Epigenetic modifications regulate gene expression. The transcription of DNA into RNA and subsequent translation into proteins determines the form and function of all living things. The level of DNA transcription generally depends on how accessible DNA is to transcription factors. Many epigenetic changes occur either on histones, which are normally associated with DNA in chromatin, or directly on the DNA. For instance, methylation of DNA leads to transcriptional silencing by denying access to transcription factors. Histone methylation can lead to either silencing or activation as determined by the amino acid marked. Meanwhile, histone acetylation typically lessens the hold of histones on DNA by reducing positive charge, resulting in facilitation of transcription (Weinhold et al. 2001).
In eukaryotes, DNA is organized with the help of histones into compact particles called nucleosomes, where sequences of about 147 DNA base pairs make ~1.65 turns around histone protein octamers. DNA within nucleosomes is inaccessible to many transcription factors. Some transcription factors, so-called pioneering factors are still able to bind their DNA binding sites on the nucleosomal DNA. For most other transcription factors, the nucleosome should be actively unwound by molecular motors such as chromatin remodelers. Alternatively, the nucleosome can be partially unwrapped by thermal fluctuations, allowing temporary access to the transcription factor binding site. In many cases, a transcription factor needs to compete for binding to its DNA binding site with other transcription factors and histones or non-histone chromatin proteins. Pairs of transcription factors and other proteins can play antagonistic roles (activator versus repressor) in the regulation of the same gene.
The innate immune system relies on germline encoded pattern recognition receptors (PRRs) to recognize distinct pathogen-associated molecular patterns (PAMPs). Upon recognition of a PAMP, PRRs generate signal cascades leading to transcription of genes associated with the immune response. Because all pathogens utilize nucleic acid to propagate, DNA and RNA can be recognized by PRRs to trigger immune activation. In normal cells, DNA is confined to the nucleus or mitochondria. The presence of DNA in the cytosol is indicative of cellular damage or infection and leads to activation of genes associated with the immune response. One way cytosolic DNA is sensed is via the cGAS/STING pathway, specifically by the cyclic-GMP-AMP synthase (cGAS). Upon DNA recognition, cGAS dimerizes and stimulates the formation of cyclic-GMP-AMP (cGAMP). cGAMP then binds directly to stimulator of interferon genes (STING) which triggers phosphorylation/activation of the transcription factor IRF3 via TBK1. IRF3 is able to enter the nucleus to promote transcription of inflammatory genes, such as IFN-β.
Within the damaged cell, the CSA protein normally localizes to sites of DNA damage, particularly inter-strand cross-links, double-strand breaks and some monoadducts. CSB protein is also normally recruited to DNA damaged sites, and its recruitment is most rapid and robust as follows: interstrand crosslinks > double-strand breaks > monoadducts > oxidative damages. CSB protein forms a complex with another DNA repair protein, SNM1A(DCLRE1A), a 5’ – 3’ exonuclease, that localizes to inter-strand cross-links in a transcription dependent manner. The accumulation of CSB protein at sites of DNA double-strand breaks occurs in a transcription dependent manner and facilitates homologous recombinational repair of the breaks. During the G0/G1 phase of the cell cycle, DNA damage can trigger a CSB-dependent recombinational repair process that uses an RNA (rather than DNA) template. 
In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. These crosslinks can, however, be repaired through excision or recombination pathways.
Elucidating the regulatory mechanisms used to govern essential cellular processes is one of the most intensely studied branches of science. Cellular regulatory networks can be incredibly complex, and often involve the coordination of multiple processes that begin with the modulation of gene expression. The binding of transcription factor molecules to DNA, either alone or in combination with other transcription factors, is used to control gene expression in response to both intra- and extracellular stimuli. Characterizing the binding mechanisms and specificities of transcription factors to specific regions of DNA – and identifying these transcription factors – is a fundamental component of the process of resolving cellular regulatory dynamics. Before the introduction of SMiLE-seq technology, ChIP-seq (chromatin immunoprecipitation sequencing) and HT-SELEX (high throughput systematic evolution of ligands by exponential enrichment) technologies were used to successfully characterize nearly 500 transcription factor-DNA binding interactions. ChIP-seq uses immunoprecipitation to isolate specific transcription factors bound to DNA fragments. Immunoprecipitation is followed by DNA sequencing, which identifies the genomic regions to which transcription factors bind. HT-SELEX, a similar method, uses random, synthetically generated DNA molecules as bait for transcription factors "in vitro". Sequence preferences and binding affinities are characterized based on successful binding interactions between bait molecules and transcription factors. While many unique transcription factor-DNA binding interactions have been characterized using these methods, it is estimated that this described fraction represents fewer than 50% of the transcription factors present in humans. The development of SMiLE-seq technology has provided an attractive alternative method with the potential to facilitate identification and characterization of previously undescribed transcription factor-DNA binding interactions.
Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally, tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways that lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of the cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. The p53 protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.
The ID4 gene is part of the ID gene family. This family is also known as inhibitors of DNA binding protein family and are composed of transcription inhibitory proteins which modulate a number of processes. They are transcriptional regulators that work by negatively regulating their basic helix-loop-helix (bHLH) transcription factors by forming heterodimers. The heterodimer is what inhibits their DNA binding and transcriptional activity.
Some noncoding DNA sequences determine where transcription factors attach. A transcription factor is a protein that binds to specific non-coding DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA.
A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.
In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein also acts as a metastasis suppressor. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.
A transcription factor is a protein that binds to specific DNA sequences (enhancer or promoter), either alone or with other proteins in a complex, to control the rate of transcription of genetic information from DNA to messenger RNA by promoting (serving as an activator) or blocking (serving as a repressor) the recruitment of RNA polymerase. As a class of protein, general transcription factors bind to promoters along the DNA sequence or form a large transcription preinitiation complex to activate transcription. General transcription factors are necessary for transcription to occur.
In the absence of hormone, estrogen receptors are largely located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, and subsequent binding of the receptor dimer to specific sequences of DNA known as hormone response elements. The DNA/receptor complex then recruits other proteins that are responsible for the transcription of downstream DNA into mRNA and finally protein that results in a change in cell function. Estrogen receptors also occur within the cell nucleus, and both estrogen receptor subtypes have a DNA-binding domain and can function as transcription factors to regulate the production of proteins.
Retinoblastoma protein (Rb) has the ability to reversibly inhibit DNA replication through transcriptional repression of DNA replication factors. Rb is able to bind to transcription factors in the E2F family and thereby inhibit their function. When Rb is chronically activated, it leads to the downregulation of the necessary DNA replication factors. Within 72–96 hours of active Rb induction in A2-4 cells, the target DNA replication factor proteins—MCMs, RPA34, DBF4, RFCp37, and RFCp140—all showed decreased levels. Along with decreased levels, there was a simultaneous and expected inhibition of DNA replication in these cells. This process, however, is reversible. Following induced knockout of Rb, cells treated with cisplatin, a DNA-damaging agent, were able to continue proliferating, without cell cycle arrest, suggesting Rb plays an important role in triggering chronic S-phase arrest in response to genotoxic stress.
Homologous recombination in functional regions of DNA is strongly stimulated by transcription, as observed in a range of different organisms. Transcription associated recombination appears to be due, at least in part, to the ability of transcription to open the DNA structure and enhance accessibility of DNA to exogenous chemicals and internal metabolites that cause recombinogenic DNA damages. These findings suggest that transcription-associated recombination may contribute significantly to recombination hotspot formation.
Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). cGAMP binds to Stimulator of Interferon Genes (STING) which triggers phosphorylation of IRF3 via TBK1. IRF3 can then go to the nucleus to trigger transcription of inflammatory genes. This pathway plays a critical role in mediating immune defense against double-stranded DNA viruses.
In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.