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Transcription (biology)

About: Transcription (biology) is a research topic. Over the lifetime, 56532 publications have been published within this topic receiving 2952782 citations. The topic is also known as: genetic transcription & transcription, genetic.


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Journal ArticleDOI
TL;DR: iNOS is identified as the first gene that requires IRF-1 for IFN-gamma-dependent transcriptional regulation, and site-specific substitution of two conserved nucleotides withinIRF-E in the context of the full-length iNOS promoter ablatedIFN- gamma's contribution to synergistic enhancement of transcription.
Abstract: Interferon gamma (IFN-gamma) interacts synergistically with bacterial lipopolysaccharide (LPS) to induce transcription of iNOS, the isoform of nitric oxide synthase whose activity is independent of elevated Ca2+ and exogenous calmodulin. To define a cis-acting element mediating IFN-gamma-dependent synergy, we made deletions in iNOS promoter constructs fused to reporter genes, transfected RAW 264.7 macrophages, and treated the cells with IFN-gamma and/or LPS. This analysis implicated the region from positions -951 to -911, a cluster of four enhancer elements known to bind IFN-gamma-responsive transcription factors, including an interferon regulatory factor binding site (IRF-E) at nucleotides -913 to -923. Site-specific substitution of two conserved nucleotides within IRF-E in the context of the full-length iNOS promoter ablated IFN-gamma's contribution to synergistic enhancement of transcription. Electromobility shift assays performed with a probe containing IRF-E revealed the existence of a complex in nuclei of RAW 264.7 macrophages that was present only after treatment with IFN-gamma, which reacted specifically with anti-IRF-1 immunoglobulin G and which included a species migrating at 40-45 kD, consistent with the apparent molecular weight of murine IRF-1. Thus, the synergistic contribution of IFN-gamma to transcription of iNOS in RAW 264.7 macrophages requires that IRF-1 bind to IRF-E in the iNOS promoter. In conjunction with the work of Kamijo et al. (Kamijo, R., H. Harada, T. Matsuyama, M. Bosland, J. Gerecitano, D. Shapiro, J. Le, K. S. Im, T. Kimura, S. Green et al. 1994. Science [Wash. DC]. 263:1612), these findings identify iNOS as the first gene that requires IRF-1 for IFN-gamma-dependent transcriptional regulation.

481 citations

Journal ArticleDOI
TL;DR: A small region in the promoter-enhancer of the interleukin-2 (Il2) gene is defined that demethylates in T lymphocytes following activation, and remains demethylated thereafter, implying that this demethylation process proceeds by an active enzymatic mechanism.
Abstract: A role for DNA demethylation in transcriptional regulation of genes expressed in differentiated somatic cells remains controversial. Here, we define a small region in the promoter-enhancer of the interleukin-2 (Il2) gene that demethylates in T lymphocytes following activation, and remains demethylated thereafter. This epigenetic change was necessary and sufficient to enhance transcription in reporter plasmids. The demethylation process started as early as 20 minutes after stimulation and was not prevented by a G1 to S phase cell cycle inhibitor that blocks DNA replication. These results imply that this demethylation process proceeds by an active enzymatic mechanism.

481 citations

Journal ArticleDOI
TL;DR: Results are consistent with transcription occurring as templates slide past attached polymerases, as nascent RNA is extruded into the factories, which the authors call transcription 'factories'.
Abstract: Nascent transcripts in permeabilized HeLa cells were elongated by approximately 30–2,000 nucleotides in Br-UTP or biotin-14-CTP, before incorporation sites were immunolabelled either pre- or post-embedding, and visualized by light or electron microscopy. Analogues were concentrated in approximately 2,100 (range 2,000-2,700) discrete sites attached to a nucleoskeleton and surrounded by chromatin. A typical site contained a cluster (diameter 71 nm) of at least 4, and probably about 20, engaged polymerases, plus associated transcripts that partially overlapped a zone of RNA polymerase II, ribonucleoproteins, and proteins rich in thiols and acidic groups. As each site probably contains many transcription units, these results suggest that active polymerases are confined to these sites, which we call transcription ‘factories’. Results are consistent with transcription occurring as templates slide past attached polymerases, as nascent RNA is extruded into the factories.

480 citations

Journal ArticleDOI
10 Jan 1975-Science
TL;DR: Identification of mutant variants of the sequence combined with the in vitro biochemical studies of others has allowed us to tentatively identify the recognition site for each of these proteins, and to suggest how CAP might act at a distance to affect the interaction of RNA polymerase with the promoter.
Abstract: The nucleotide sequence of the lac promoter-operator region has been determined. The 122 base pairs comprising this region include the recognition sites for RNA polymerase, the positive regulatory protein, CAP, and the negative regulatory protein, the repressor. Identification of mutant variants of the sequence combined with the in vitro biochemical studies of others has allowed us to tentatively identify the recognition site for each of these proteins, and to suggest how CAP might act at a distance to affect the interaction of RNA polymerase with the promoter.

480 citations

Journal ArticleDOI
TL;DR: The data support a model in which the differential association of Runx1 with Foxp3 and with RORγt regulates TH-17 differentiation, and suggest that optimal transcription of the gene encoding interleukin 17 required a 2-kilobase promoter and at least one conserved noncoding sequence, CNS-5.
Abstract: The molecular mechanisms underlying the differentiation of interleukin 17-producing T helper cells (T(H)-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors RORgammat and Runx1. Runx1 influenced T(H)-17 differentiation by inducing RORgammat expression and by binding to and acting together with RORgammat during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on T(H)-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORgammat regulates T(H)-17 differentiation.

480 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20229
20211,730
20201,721
20191,686
20181,571
20171,465