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Transcriptionally Regulatory Sequences of Phylogenetic Significance
Published in S. K. Dutta, DNA Systematics, 2019
For RNA polymerase II, at least 5 factors are essential and sufficient for accurate initiation at Ad2 major late promoters in a relatively crude cell extract.246,247 One, TFIIC, purified to homogeneity, inhibits random transcription in crude systems but is not required in more purified systems. The presence of another, TFIIA, maximizes the transcription level, presumably due to its carrying an RNase inhibitor. The others are factors which bind to RNA polymerase (TFIIB), ATPase (TFIIE), or the template (TFIID). The hydrolysis of ATP by ATPase is presumably important in the initiation step. However, the requirement of these factors apparently applies only to certain late promoters.
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.
Epigenetic control of skin immunity
Published in Immunological Medicine, 2023
Human cells contain two meters of genomic DNA that is tightly folded and packed within the nucleus. Genomic DNA forms a secondary structure referred to as chromatin that fits into a limited space [7]. The basic unit of chromatin, the nucleosome, is consisted of 147 bp genomic DNA and a core histone octamer. DNA is negatively charged and histones are positively charged, and the opposing charges allow DNA to wrap itself tightly around the histone octamer to form a nucleosome. Initiation of transcription requires the binding of RNA polymerase II and several basic transcription factors, called TFIIA and TFIIB, bind to promoters located near the transcription start sites [8]. Sequence-specific DNA-binding transcription factors (TFs) are involved in the enhancement of transcription. TFs bind to enhancers and cause genomic DNA to form looped structures that shorten the distance between enhancers and promoters, thereby promoting the transcription of the target genes. Transcriptional activity is also closely related to the degree of DNA condensation associated with chromatin structure [6,8]. Tightly packed chromatin, called closed chromatin or heterochromatin, restricts the access of RNA polymerase II and the transcription factors to the regulatory sites, and consequently, suppresses the expression of target genes. Open chromatin or euchromatin that is less condensed allows easier access of the transcriptional machinery to DNA, thus setting target genes to be more actively transcribed.
Targeting transcription factors in multiple myeloma: evolving therapeutic strategies
Published in Expert Opinion on Investigational Drugs, 2019
Shirong Li, Sonia Vallet, Antonio Sacco, Aldo Roccaro, Suzanne Lentzsch, Klaus Podar
Basal gene transcription is initiated by the formation of the pre-initiation complex at the core promoter, which is composed of general TFs (TFIIA, TFIIB, TFIIE, TFIIF and TFIIH); the Mediator co-activator complex; and Pol II. Differential gene transcription is achieved by specific TFs (e.g. AP-1, C/EBP, ATF/CREB, c-Myc and SP-1) that bind to the proximal promoter or super/enhancer sequences and recruit co-factors (co-activators or co-repressors). Formation of these complexes enables differential gene expression in a spatio- temporal manner. While the core promoter contains the transcription start site; the proximal promoter is located within 2kb upstream of the transcription start site; and enhancers or super-enhancers are located 2 to 100kb up- or downstream from the promoter, sometimes also within introns or downstream the poly-A site. Chromatin loops physically juxtapose proximal promoters and super/enhancers to the core promoter of the target gene. They thereby form insulated neighborhoods that are flanked by insulators, boundary elements, which bind 11-zinc finger protein or CCCTC-binding factor (CTCF) proteins and the cohesion complex. Insulated neighborhoods warrant sequestration and insulation of specific target genes, its transcription apparatus, and regulatory elements in order to prevent binding of TF complexes of its enhancers to promoters of flanking genes. Master or lineage-defining TFs control gene expression programs that define cell identity; and signal- activated TFs adapt the cell to extra- and intracellular signals. Signals from the microenvironment are integrated through the ability of master TFs to recruit signal- activated TFs to SE sites. Activated cell membrane receptors induce second messenger signaling cascades ultimately resulting in the phosphorylation of either resident nuclear TFs (e.g. AP-1) or latent cytoplasmic TFs, which translocate into the nucleus when activated (e.g. Stat-3, NF-kB). Similar to biological stimuli also environmental stimuli such as hypoxia and high temperatures activate signaling cascades and downstream TFs, e.g. hypoxia inducible factor (HIF). lncRNAs and siRNAs, themselves products of transcriptions, are major regulators of the transcriptional process. They function through binding to TFs, histone-modifying complexes, CTCF and RNA polymerase II. Transcription elongation is regulated via recruitment of P-TEFb, a RNA Pol II regulatory complex containing CDK9 and Cyclin1 [1,2].