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Upstream activating sequence

About: Upstream activating sequence is a research topic. Over the lifetime, 1633 publications have been published within this topic receiving 100112 citations.


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Journal ArticleDOI
01 Jan 1985-Nature
TL;DR: It is suggested that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo.
Abstract: The human genome is rich in sequences which are structurally related to the 7SL RNA component of the signal recognition particle. The 7SL DNA sequence family consists of four 7SL genes, 500 7SL pseudogenes (which are truncated at one or both ends of the 7SL sequence) and 500,000 Alu sequences. Both 7SL genes and Alu elements are transcribed by RNA polymerase III, and we show here that the internal 7SL promoter lies within the Alu-like part of the 7SL gene. Why then does RNA polymerase III transcribe the few 7SL genes so efficiently, while transcripts from the far more abundant Alu elements are not readily detectable? We find that a human 7SL gene and a synthetic Alu sequence derived from it are expressed 50-100-fold more efficiently in vitro than either a representative Alu element or two 7SL pseudogenes. 5' Deletion and insertion mutants of the 7SL gene demonstrate that, in conjunction with the internal promoter, the first 37 nucleotides upstream from the transcription start site are essential for efficient and accurate initiation in vitro. We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo. This may help to explain the homogeneity of the Alu family within each mammalian genome, as well as the species-specific differences between mammalian Alu families.

154 citations

Journal ArticleDOI
TL;DR: The results suggest that the sin4 delta mutation may alter the structure of chromatin, and these changes in chromatin structure may affect transcriptional regulation.
Abstract: We have cloned and sequenced the SIN4 gene and determined that SIN4 is identical to TSF3, identified as a negative regulator of GAL1 gene transcription (S. Chen, R.W. West, Jr., S.L. Johnson, H. Gans, and J. Ma, submitted for publication). Yeast strains bearing a sin4 delta null mutation have been constructed and are temperature sensitive for growth and display defects in both negative and positive regulation of transcription. Transcription of the CTS1 gene is reduced in sin4 delta mutants, suggesting that Sin4 functions as a positive transcriptional regulator. Additionally, a Sin4-LexA fusion protein activates transcription from test promoters containing LexA binding sites. The sin4 delta mutant also shows phenotypes common to histone and spt mutants, including suppression of delta insertion mutations in the HIS4 and LYS2 promoters, expression of promoters lacking upstream activation sequence elements, and decreased superhelical density of circular DNA molecules. These results suggest that the sin4 delta mutation may alter the structure of chromatin, and these changes in chromatin structure may affect transcriptional regulation.

153 citations

Journal ArticleDOI
TL;DR: Two DNA elements are identified in the prealbumin gene that respond in a cell-specific manner: a proximal promoter including a crucial sequence between -108 and -151 nucleotides and a distant enhancer element located between 1.6 and 2.15 kilobases upstream.
Abstract: The mouse genomic clone for the prealbumin (transthyretin) gene was cloned, and its upstream regulatory regions were analyzed. The 200 nucleotides 5' to the cap site when placed within a recombinant plasmid were sufficient to direct transient expression in HepG2 (human hepatoma) cells, but this DNA region did not support expression in HeLa cells. The sequence of the 200-nucleotide region is highly conserved between mouse and human DNA and can be considered a cell-specific promoter. Deletions of this promoter region identified a crucial element for cell-specific expression between 151 and 110 nucleotides 5' to the RNA start site. A region situated at about 1.6 to 2.15 kilobases upstream of the RNA start site was found to stimulate expression 10-fold in HepG2 cells but not in HeLa cells. This far upstream element was invertible and increased expression from the beta-globin promoter in HepG2 cells. Unlike the simian virus 40 enhancer, the prealbumin enhancer would not stimulate beta-globin synthesis in HeLa cells, and even the simian virus 40 enhancer did not stimulate the prealbumin promoter in HeLa cells. Thus, we identified in the prealbumin gene two DNA elements that respond in a cell-specific manner: a proximal promoter including a crucial sequence between -108 and -151 nucleotides and a distant enhancer element located between 1.6 and 2.15 kilobases upstream.

153 citations

Journal ArticleDOI
TL;DR: The results show that this chimeric plasmid construct exhibits appropriate activation and coordinate expression with the endogenous SERCA2 gene during the terminal differentiation of myoblasts into myotubes, suggesting that it contains the promoter and upstream sequence elements required for the regulated expression of the SER CA2 gene.

152 citations

Journal ArticleDOI
TL;DR: In vitro DNA-binding experiments with purified E2 and TFIIDs showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site.
Abstract: The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters. To further understand the mechanisms by which the same transcription factor may act differentially, the full-length BPV-1 E2 protein was expressed and purified from yeast and assayed in vitro for its capacity to modulate transcription. E2 stimulated transcription of the HSV thymidine kinase (TK) promoter when E2-binding sites were positioned in an enhancer configuration approximately 100 bp upstream of the promoter start site. In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter. This repression was mediated through binding to the E2 DNA-binding site immediately upstream of the P105 promoter TATA box and could be abrogated by preincubation of the HPV-18 P105 promoter template with the nuclear extract allowing the formation of the preinitiation complex. In vitro DNA-binding experiments with purified E2 and TFIID showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site. In these respects, E2 is similar to the bacteriophage lambda repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences.

152 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20232
20223
20218
20206
20196
20186