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Journal ArticleDOI

The core promoter: At the heart of gene expression.

01 Aug 2015-Biochimica et Biophysica Acta (Biochim Biophys Acta)-Vol. 1849, Iss: 8, pp 1116-1131
TL;DR: A broad spectrum of studies that highlight the importance of the core promoter and its pivotal role in the regulation of metazoan gene expression are reviewed and future research directions and challenges are suggested.
About: This article is published in Biochimica et Biophysica Acta.The article was published on 2015-08-01. It has received 140 citations till now. The article focuses on the topics: Enhancer RNAs & Transcription factor II D.
Citations
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Journal ArticleDOI
TL;DR: An extensive catalog of nascent and steady-state transcripts in Arabidopsis thaliana seedlings was generated using global nuclear run-on sequencing, 5′GRO-seq, and RNA-seq and published maize data to capture characteristics of plant transcription to provide insight into plant transcription and eukaryotic gene expression as a whole.
Abstract: Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steady-state transcripts in Arabidopsis thaliana seedlings using global nuclear run-on sequencing (GRO-seq), 5′GRO-seq, and RNA-seq and reanalyzed published maize data to capture characteristics of plant transcription. De novo annotation of nascent transcripts accurately mapped start sites and unstable transcripts. Examining the promoters of coding and noncoding transcripts identified comparable chromatin signatures, a conserved “TGT” core promoter motif and unreported transcription factor-binding sites. Mapping of engaged RNA polymerases showed a lack of enhancer RNAs, promoter-proximal pausing, and divergent transcription in Arabidopsis seedlings and maize, which are commonly present in yeast and humans. In contrast, Arabidopsis and maize genes accumulate RNA polymerases in proximity of the polyadenylation site, a trend that coincided with longer genes and CpG hypomethylation. Lack of promoter-proximal pausing and a higher correlation of nascent and steady-state transcripts indicate Arabidopsis may regulate transcription predominantly at the level of initiation. Our findings provide insight into plant transcription and eukaryotic gene expression as a whole.

128 citations


Cites background from "The core promoter: At the heart of ..."

  • ...At the core promoter, located approximately ±50 bp relative to the TSS, basal TFs cooperate with conserved DNA sequence motifs to orchestrate recruitment of the RNA polymerase (RNAP) (1, 3)....

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Journal ArticleDOI
TL;DR: An expanded view of the core promoter that comprises the classical DNA sequence motifs, sequence-specific DNA-binding transcription factors, chromatin signals, and DNA structure is described.
Abstract: The signals that direct the initiation of transcription ultimately converge at the core promoter, which is the gateway to transcription. Here we provide an overview of the RNA polymerase II core promoter in bilateria (bilaterally symmetric animals). The core promoter is diverse in terms of its composition and function yet is also punctilious, as it acts with strict rules and precision. We additionally describe an expanded view of the core promoter that comprises the classical DNA sequence motifs, sequence-specific DNA-binding transcription factors, chromatin signals, and DNA structure. This model may eventually lead to a more unified conceptual understanding of the core promoter.

117 citations


Cites background from "The core promoter: At the heart of ..."

  • ...The initiation of Pol II transcription is mediated by a stretch of DNA known as the core promoter (for reviews, see Smale and Kadonaga 2003; Goodrich and Tjian 2010; Kadonaga 2012; Lenhard et al. 2012; Danino et al. 2015; Roy and Singer 2015)....

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Journal ArticleDOI
TL;DR: The recent advances in synthetic promoters and TFs in plants are reviewed and a speculate on their future is speculated.

116 citations


Cites background from "The core promoter: At the heart of ..."

  • ...The core promoter directs accurate transcription initiation when bound by some basal TFs, and provides little or no basal expression level [14 ,15]....

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Journal ArticleDOI
TL;DR: This work further develops the deep learning approach that was relatively successful to discriminate short promoter and non-promoter sequences and predicts the exact positions of the TSS inside the genomic sequences testing every possible location.
Abstract: Motivation Computational identification of promoters is notoriously difficult as human genes often have unique promoter sequences that provide regulation of transcription and interaction with transcription initiation complex. While there are many attempts to develop computational promoter identification methods, we have no reliable tool to analyze long genomic sequences. Results In this work, we further develop our deep learning approach that was relatively successful to discriminate short promoter and non-promoter sequences. Instead of focusing on the classification accuracy, in this work we predict the exact positions of the transcription start site inside the genomic sequences testing every possible location. We studied human promoters to find effective regions for discrimination and built corresponding deep learning models. These models use adaptively constructed negative set, which iteratively improves the model's discriminative ability. Our method significantly outperforms the previously developed promoter prediction programs by considerably reducing the number of false-positive predictions. We have achieved error-per-1000-bp rate of 0.02 and have 0.31 errors per correct prediction, which is significantly better than the results of other human promoter predictors. Availability and implementation The developed method is available as a web server at http://www.cbrc.kaust.edu.sa/PromID/.

81 citations

Journal ArticleDOI
30 Jul 2015
TL;DR: The Elements Navigation Tool (ElemeNT) is a user-friendly web-based, interactive tool for prediction and display of putative core promoter elements and their biologically-relevant combinations, and the CORE database summarizes ElemeNT-predicted core promoter Elements near CAGE and RNA-seq-defined Drosophila melanogaster transcription start sites (TSSs).
Abstract: Core promoter elements play a pivotal role in the transcriptional output, yet they are often detected manually within sequences of interest. Here, we present 2 contributions to the detection and curation of core promoter elements within given sequences. First, the Elements Navigation Tool (ElemeNT) is a user-friendly web-based, interactive tool for prediction and display of putative core promoter elements and their biologically-relevant combinations. Second, the CORE database summarizes ElemeNT-predicted core promoter elements near CAGE and RNA-seq-defined Drosophila melanogaster transcription start sites (TSSs). ElemeNT's predictions are based on biologically-functional core promoter elements, and can be used to infer core promoter compositions. ElemeNT does not assume prior knowledge of the actual TSS position, and can therefore assist in annotation of any given sequence. These resources, freely accessible at http://lifefaculty.biu.ac.il/gershon-tamar/index.php/resources, facilitate the identification of core promoter elements as active contributors to gene expression.

71 citations


Cites background from "The core promoter: At the heart of ..."

  • ...Although it was previously believed that the core promoter is a universal component that works in a similar mechanism for all protein-coding genes, it is nowadays established that core promoters differ in their architecture and function.(3,4,7-10) Moreover, distinct core promoter compositions were demonstrated to result in diverse transcriptional outputs....

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References
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Journal ArticleDOI
TL;DR: The RNA-Seq approach to transcriptome profiling that uses deep-sequencing technologies provides a far more precise measurement of levels of transcripts and their isoforms than other methods.
Abstract: RNA-Seq is a recently developed approach to transcriptome profiling that uses deep-sequencing technologies. Studies using this method have already altered our view of the extent and complexity of eukaryotic transcriptomes. RNA-Seq also provides a far more precise measurement of levels of transcripts and their isoforms than other methods. This article describes the RNA-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes.

11,528 citations


Additional excerpts

  • ...Insights are gained from studies of specific genes and gene networks [13-15], as well as from genome-wide studies [11, 16] utilizing methodologies such as PEAT [17], 5' RACE [18], CAGE [19], FAIRE-seq [20], ChIP-seq [21], Gro-seq [22], and RNA-seq [23], and key projects and consortia (e....

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  • ...Insights are gained from studies of specific genes and gene networks [13-15], as well as from genome-wide studies [11, 16] utilizing methodologies such as PEAT [17], 5' RACE [18], CAGE [19], FAIRE-seq [20], ChIP-seq [21], Gro-seq [22], and RNA-seq [23], and key projects and consortia (e.g. modENCODE [24], ENCODE [25] and FANTOM5 [26]), which developed following the implementation of some of the above methods....

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Journal ArticleDOI
TL;DR: The efficacy of this cDNA cloning strategy was demonstrated by isolating cDNA clones of mRNA from int-2, a mouse gene that expresses four different transcripts at low abundance, the longest of which is approximately 2.9 kilobases.
Abstract: We have devised a simple and efficient cDNA cloning strategy that overcomes many of the difficulties encountered in obtaining full-length cDNA clones of low-abundance mRNAs. In essence, cDNAs are generated by using the DNA polymerase chain reaction technique to amplify copies of the region between a single point in the transcript and the 3' or 5' end. The minimum information required for this amplification is a single short stretch of sequence within the mRNA to be cloned. Since the cDNAs can be produced in one day, examined by Southern blotting the next, and readily cloned, large numbers of full-length cDNA clones of rare transcripts can be rapidly produced. Moreover, separation of amplified cDNAs by gel electrophoresis allows precise selection by size prior to cloning and thus facilitates the isolation of cDNAs representing variant mRNAs, such as those produced by alternative splicing or by the use of alternative promoters. The efficacy of this method was demonstrated by isolating cDNA clones of mRNA from int-2, a mouse gene that expresses four different transcripts at low abundance, the longest of which is approximately 2.9 kilobases. After less than 0.05% of the cDNAs produced had been screened, 29 independent int-2 clones were isolated. Sequence analysis demonstrated that the 3' and 5' ends of all four int-2 mRNAs were accurately represented by these clones.

4,673 citations


Additional excerpts

  • ...Insights are gained from studies of specific genes and gene networks [13-15], as well as from genome-wide studies [11, 16] utilizing methodologies such as PEAT [17], 5' RACE [18], CAGE [19], FAIRE-seq [20], ChIP-seq [21], Gro-seq [22], and RNA-seq [23], and key projects and consortia (e....

    [...]

  • ...Insights are gained from studies of specific genes and gene networks [13-15], as well as from genome-wide studies [11, 16] utilizing methodologies such as PEAT [17], 5' RACE [18], CAGE [19], FAIRE-seq [20], ChIP-seq [21], Gro-seq [22], and RNA-seq [23], and key projects and consortia (e.g. modENCODE [24], ENCODE [25] and FANTOM5 [26]), which developed following the implementation of some of the above methods....

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Journal ArticleDOI
23 Feb 2007-Cell
TL;DR: This Review highlights advances in the understanding of chromatin regulation and discusses how such regulation affects the binding of transcription factors as well as the initiation and elongation steps of transcription.

3,424 citations

Journal ArticleDOI
TL;DR: This work has provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).
Abstract: Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).

2,446 citations


"The core promoter: At the heart of ..." refers background in this paper

  • ...subunit that in turn reaches the first codon, AUG, via a 5' UTR scanning mechanism (reviewed in [249])....

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Journal ArticleDOI
08 Jun 2007-Science
TL;DR: Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes and support a highly interleaved organization of the human transcriptome.
Abstract: Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.

2,312 citations

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