A code for transcription initiation in mammalian genomes

Frith, Martin C.; Valen, Eivind; Krogh, Anders; Hayashizaki, Yoshihide; Carninci, Piero; Sandelin, Albin

doi:10.1101/gr.6831208

Cited by 259 publications

(288 citation statements)

References 59 publications

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“…This result indicates that TSS distributions are innate aspects of promoters, rather than dynamically controlled transcriptional modes. This is consistent with the finding of Frith et al (2008) that TSS distributions in mammalian promoters, as determined by CAGE, can be predicted from the local DNA sequence. Thus, it may be that the TSS distribution of a promoter can be entirely characterized by assaying at a single biological sample in which the promoter is active.…”

Section: Discussionsupporting

confidence: 92%

Genome-wide analysis of promoter architecture in Drosophila melanogaster

Hoskins

Landolin²,

Brown³

et al. 2010

Genome Res.

Self Cite

226

344

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Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.

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Section: Discussionsupporting

confidence: 92%

Genome-wide analysis of promoter architecture in Drosophila melanogaster

Hoskins

Landolin²,

Brown³

et al. 2010

Genome Res.

Self Cite

226

344

View full text Add to dashboard Cite

show abstract

“…Interestingly, those with adjacent dominant start sites display a GGG consensus sequence and weak TATA conservation, and those with TSS sites separated by a single nucleotide also exhibit a relatively strong GGG preference and strong TATA use (49). Importantly, TSS use varied among cell types and between normal and tumoral cell lines, indicating that factors other than sequence are important for TSS selection (49,50). Thus it is conceivable that HIV-1 TSS use may be affected by intracellular conditions or change temporally during replication, enabling early production of the longer Cap 2G/ Cap 3G mRNAs used for viral protein synthesis followed by an increase in the production of Cap 1G gRNA transcripts relegated for packaging.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome

Kharytonchyk

Monti

Smaldino

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

119

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The promoter in HIV type 1 (HIV-1) proviral DNA contains three sequential guanosines at the U3-R boundary that have been proposed to function as sites for transcription initiation. Here we show that all three sites are used in cells infected with HIV-1 and that viral RNAs containing a single 5′ capped guanosine ( Cap 1G) are specifically selected for packaging in virions, consistent with a recent report [Masuda et al. (2015) Sci Rep 5:17680]. In addition, we now show that transcripts that begin with two or three capped guanosines ( Cap 2G or Cap 3G) are enriched on polysomes, indicating that RNAs synthesized from different transcription start sites have different functions in viral replication. Because genomes are selected for packaging as dimers, we examined the in vitro monomer-dimer equilibrium properties of Cap 1G, Cap 2G, and Cap 3G 5′-leader RNAs in the NL4-3 strain of HIV-1. Strikingly, under physiological-like ionic conditions in which the Cap 1G 5′-leader RNA adopts a dimeric structure, the Cap 2G and Cap 3G 5′-leader RNAs exist predominantly as monomers. Mutagenesis studies designed to probe for base-pairing interactions suggest that the additional guanosines of the 2G and 3G RNAs remodel the base of the PolyA hairpin, resulting in enhanced sequestration of dimerpromoting residues and stabilization of the monomer. Our studies suggest a mechanism through which the structure, function, and fate of the viral genome can be modulated by the transcriptionally controlled presence or absence of a single 5′ guanosine.HIV-1 | 5′-leader | transcription | RNA | structure

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“…Previous computational studies of promoter regions upstream of similar TSS initiation patterns in animals have shown that it is possible to predict the locations of NP TSSs from DNA sequence (Frith et al, 2008;Megraw et al, 2009;Rach et al, 2011). A machine learning model called S-Peaker (Megraw et al, 2009) was constructed to use sequence content along with the position specificity and binding affinity of TFBSs to reveal which factors are important for achieving a sharp spatial peak of transcription.…”

Section: Distinct Patterns Of Transcription Initiation Exist In Plantsmentioning

confidence: 99%

Paired-End Analysis of Transcription Start Sites in Arabidopsis Reveals Plant-Specific Promoter Signatures

et al. 2014

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Understanding plant gene promoter architecture has long been a challenge due to the lack of relevant large-scale data sets and analysis methods. Here, we present a publicly available, large-scale transcription start site (TSS) data set in plants using a high-resolution method for analysis of 59 ends of mRNA transcripts. Our data set is produced using the paired-end analysis of transcription start sites (PEAT) protocol, providing millions of TSS locations from wild-type Columbia-0 Arabidopsis thaliana whole root samples. Using this data set, we grouped TSS reads into "TSS tag clusters" and categorized clusters into three spatial initiation patterns: narrow peak, broad with peak, and weak peak. We then designed a machine learning model that predicts the presence of TSS tag clusters with outstanding sensitivity and specificity for all three initiation patterns. We used this model to analyze the transcription factor binding site content of promoters exhibiting these initiation patterns. In contrast to the canonical notions of TATA-containing and more broad "TATA-less" promoters, the model shows that, in plants, the vast majority of transcription start sites are TATA free and are defined by a large compendium of known DNA sequence binding elements. We present results on the usage of these elements and provide our Plant PEAT Peaks (3PEAT) model that predicts the presence of TSSs directly from sequence.

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A code for transcription initiation in mammalian genomes

Cited by 259 publications

References 59 publications

Genome-wide analysis of promoter architecture in Drosophila melanogaster

Genome-wide analysis of promoter architecture in Drosophila melanogaster

Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome

Paired-End Analysis of Transcription Start Sites in Arabidopsis Reveals Plant-Specific Promoter Signatures

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