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Introduction to Molecular Biology
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Unlike prokaryote, eukaryotes require transcription factors to initiate transcription process. The transcription factors must bind the promoter region in DNA and form an appropriate initiation complex before the initiation of the transcription. In eukaryotic cells, three types of RNA polymerases (RNA polymerase I, II, and III) are involved in this process. The promoter region is constituted of specific nucleic acid sequence recognized by the polymerase. There are various types of promoters, such as the TATA box or the CATT box promoter regions, but all of them contain the specific sequence referred to as the starting site of transcription. In the vast majority of eukaryotic genes, the RNA polymerase II is responsible of the initiation of transcription. For the correct initiation of the transcription, the transcription factors must interact with the promoter region in a specific order. For example, in order to bind to the promoter region and initiate transcription efficiently, the DNA polymerase II (Fig. 10) requires transcription factors: TFIID, TFIIA, TFIIB, TFIIF, and TFIIE (Transcription Factor for Polymerase II). After the arrival of the transcription factors, the polymerase II can bind to the promoter region and begin the transcription. Usually, the promoters for the genes transcribed by the RNA polymerases are situated upstream from the transcription start points, with some exceptions such as the genes transcribed by the RNA polymerase III.
TP53 in cancer origin and treatment
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
Elena A. Komarova, Peter M. Chumakov, Andrei V. Gudkov
The mechanism of TP53-mediated growth arrest and apoptosis is determined, at least in part, by the activity of TP53 as a transcription factor and is dependent on TP53 binding to specific DNA elements located near the promoter regions of TP53 responsive genes. A modification of the C-terminal part of the molecule, initiated by various stress mechanisms, is followed by a conformational rearrangement and acquisition of the ability of the protein to associate with DNA. A complex interaction of the TP53 N-terminal transcription-activator region with components of the transcription apparatus such as proteins of the TFIID complex: TBP (TATA-Box Binding Protein) and TBP-associated factors TAFII, is essential (Liu et al., 1993; Lu and Levine, 1995; Seto et al., 1992; Thut et al., 1995; Truant et al., 1993). In addition, the transcription coactivators, CREB-binding protein (CBP) and its closely related p300 protein, are required in a complex with TFIID for activation of the specific promoters. p300/CBP displays histone-acetyl-transferase activity. It is able to directly interact with the RNA-polymerase II complex conducting initiation of transcription in response to the association with a transcription factor.
Progressive multifocal leukoencephalopathy
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Eric M. L. Williamson, Joseph R. Berger
Nuclear DNA-binding proteins that selectively interact with the regulatory region of the genome are critical to the tropism of JC virus. To explain the neurotropism of JCV for glial cells, experiments have concentrated on identifying nuclear DNA-binding proteins that selectively interact with said regulatory region. It is assumed that such proteins would bind specific cis-acting nucleotide base pairs (np) for control of JCV transcription. Using techniques of gel retention, protein-DNA cross-linking, and DNase footprint analysis, sequences were identified in the regulatory region at nucleotides (nt) 33–58 on the viral genome map [58]. Because the regulatory region comprises direct tandem repeats of 98 nucleotide pairs each, these binding sites exist twice, once in both repeats. Two other series of nucleotide pairs were also identified as binding sites for nuclear proteins, located on either side of nt 33–58. One of these areas, directly next to the sequences necessary for DNA replication, in the direction of the T protein-coding region, is rich in repeated AT sequences that are known to function as RNA start sites [23,39,59–61]. The protein that binds these sequences is the TFIID transcription factor represented in almost all eukaryotic cells [62]. The other protein-binding site covers an area that includes the transcriptional enhancer for JCV in as much as its sequence is similar, but not identical, to sequences previously described for this function [63]. Notably, nuclear extracts from nonpermissive cells demonstrated some binding to these regions. The functional consequence of this binding appears to downregulate JCV activity in these cells [24]. Therefore, it seems that there are proteins that positively regulate JCV expression and those that block expression in a cell type-specific manner.
Developments in drug design strategies for bromodomain protein inhibitors to target Plasmodium falciparum parasites
Published in Expert Opinion on Drug Discovery, 2020
Hanh H. T. Nguyen, Lee M. Yeoh, Scott A. Chisholm, Michael F. Duffy
The essential bromodomain protein 1 (PfBDP1) interacts with PfBDP2 and is required for expression of many genes including the coordinated expression of erythrocyte-invasion genes [53]. PfBDP1 is recruited to a subset of these invasion genes by the transcription factor ApiAP2-I [54]. Little is known about the functions of the remaining PfBDPs; PfSET1 contains a predicted SET (Su(var), enhancer of zeste, trithorax) histone methyltransferase domain, and interference with PfSET1 transcription during the asexual blood stage leads to down-regulation of many genes [40]. PfTAF1 is a putative homologue of the TFIID (transcription factor II D) complex member TAF1 (TATA-binding protein-associated factor 1) based on the predicted tertiary structure [55]. The BRD of PfTAF2 (PF3D7_0724700) is the P. falciparum orthologue of the predicted T. gondii TFIID complex member TAF2 (Figure 2).
Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus
Published in Renal Failure, 2020
Shumin Bao, Yan Guo, Zongli Diao, Weikang Guo, Wenhu Liu
According to the network diagram, these lncRNAs may regulate the expression of TFs, including STAT1, KAT2A, GATA2, TAF7 and REST. Cellular homeostasis is regulated by various signaling proteins which contribute to the activation of intracellular and extracellular cascade reactions. This, in turn, leads to the regulation of gene activity. One of the most important signal systems is the STAT family, consisting of seven members and serving as effective transcription factors to transmit cytokine and growth factor signals to the nucleus. The first member of this family to be identified and studied is STAT1, a 91 kDa protein of great importance to immune cells and other cell types [39]. STAT1 was found to exert unique, noncanonical functions such as acting as a cytoplasmic attenuator of Runx2. In this way, STAT1 is related to Runx2 and thus to osteoblast differentiation [40]. TAF7 is a component of the TFIID complex in charge of controlling the first steps of transcription, which is consistent with its essential role in cell proliferation [41]. Our study suggested that many of the lncRNAs are related to TFs, as mentioned above and these TFs may be associated with the occurrence of osteogenic differentiation induced by high phosphorus.
Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy
Published in OncoImmunology, 2018
Anne Holtorf, Anja Conrad, Bernhard Holzmann, Klaus-Peter Janssen
RNA was prepared from fresh-frozen patient or mouse tissue using RNeasy mini kit (QIAGEN). First-strand cDNA was synthesized from 1 mg total RNA using Reverse Transcription Kit (Fermentas, Thermo Fisher Scientific, Waltham, MS, USA). Quantitative RT-PCR analyses were performed using the Universal ProbeLibrary (Roche Diagnostics, Rotkreuz, Switzerland). mRNA expression levels were normalized to those of TFIID and were displayed as fold change relative to small intestine of WT mice. Oligonucleotide primers for quantitative RT-PCR were synthesized by Metabion (Martinsried, Germany). Accumulation of PCR amplification products was quantified on a LightCycler 480 Real-Time PCR system (Roche Diagnostics, Rotkreuz, Switzerland).