Identification of the human DPR core promoter element using machine learning
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139635 | GEO | 2020/06/04
REPOSITORIES: GEO
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Project description:The RNA polymerase II core promoter is the site of convergence of the signals that lead to the initiation of transcription. Here, we perform a comparative analysis of the downstream core promoter region (DPR) in Drosophila and humans by using machine learning. These studies revealed a distinct human-specific version of the DPR and led to the use of the machine learning models for the identification of synthetic extreme DPR motifs with specificity for human transcription factors relative to Drosophila factors, and vice versa. More generally, machine learning models could be analogously used to design synthetic promoter elements with customized functional properties.
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Project description:RNA Polymerase II (Pol II) carries out transcription of both protein-coding and non-coding genes. Whereas Pol II initiation at protein-coding genes has been studied in detail, Pol II initiation at non-coding genes such as small nuclear RNA (snRNA) genes is not understood at the structural level. Here we study Pol II initiation at snRNA gene promoters and show that the snRNA-activating protein complex (SNAPc) enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro. We then resolve cryo-EM structures of the SNAPc-containing Pol II preinitiation complex (PIC) assembled on U1 and U5 snRNA promoters. The core of SNAPc binds two turns of DNA and recognizes the snRNA promoter-specific proximal sequence element (PSE) located upstream of the TATA box-binding protein TBP. Two extensions of SNAPc called wing-1 and wing-2 bind TFIIA and TFIIB, respectively, explaining how SNAPc directs Pol II to snRNA promoters. Comparison of structures of closed and open promoter complexes elucidates TFIIH-independent DNA opening. These results provide the structural basis of Pol II initiation at non-coding RNA gene promoters.
2023-03-11 | PXD033638 | Pride
Project description:Control of RNA transcription is critical for the development and homeostasis of all organisms, and can occur at multiple steps of the transcription cycle, including RNA polymerase II (Pol II) recruitment, initiation, promoter-proximal pausing, and elongation. That Pol II accumulates on many promoters in metazoans implies that steps other than Pol II recruitment are rate-limiting and regulated 1-6. By integrating genome-wide Pol II chromatin immunoprecipition (ChIP) and Global Run-On (GRO) genomic data sets from Drosophila cells, we examined critical features of Pol II near promoters. The accumulation of promoter-proximal polymerase is widespread, occurring on 70% of active genes; and unlike elongating Pol II within the body of genes, promoter Pol II are held paused by factors like NELF, unable to transcribe unless nuclei are treated with strong detergent. Notably, we find that the vast majority of promoter-proximal Pol II detected by ChIP are paused, thereby identifying the biochemical nature of this rate-limiting step in transcription. Finally, we demonstrate that Drosophila promoters do not have the upstream divergent Pol II that is seen so broadly and prominently on mammalian promoters. We postulate this is a consequence of Drosophila’s extensive use of directional core promoter sequence elements, which contrasts with mammals’ lack of directional elements and prevalence of CpG island core promoters. In support of this idea, we show that the fraction of mammalian promoters containing a TATA box core element is dramatically depleted of upstream divergent transcription. ChIP-seq data set for Pol II (rpb3) (2 replicates).
2012-10-25 | E-GEOD-23542 | biostudies-arrayexpress
Project description:Control of RNA transcription is critical for the development and homeostasis of all organisms, and can occur at multiple steps of the transcription cycle, including RNA polymerase II (Pol II) recruitment, initiation, promoter-proximal pausing, and elongation. That Pol II accumulates on many promoters in metazoans implies that steps other than Pol II recruitment are rate-limiting and regulated 1-6. By integrating genome-wide Pol II chromatin immunoprecipition (ChIP) and Global Run-On (GRO) genomic data sets from Drosophila cells, we examined critical features of Pol II near promoters. The accumulation of promoter-proximal polymerase is widespread, occurring on 70% of active genes; and unlike elongating Pol II within the body of genes, promoter Pol II are held paused by factors like NELF, unable to transcribe unless nuclei are treated with strong detergent. Notably, we find that the vast majority of promoter-proximal Pol II detected by ChIP are paused, thereby identifying the biochemical nature of this rate-limiting step in transcription. Finally, we demonstrate that Drosophila promoters do not have the upstream divergent Pol II that is seen so broadly and prominently on mammalian promoters. We postulate this is a consequence of Drosophila’s extensive use of directional core promoter sequence elements, which contrasts with mammals’ lack of directional elements and prevalence of CpG island core promoters. In support of this idea, we show that the fraction of mammalian promoters containing a TATA box core element is dramatically depleted of upstream divergent transcription.
2012-10-25 | GSE23543 | GEO
Project description:Control of RNA transcription is critical for the development and homeostasis of all organisms, and can occur at multiple steps of the transcription cycle, including RNA polymerase II (Pol II) recruitment, initiation, promoter-proximal pausing, and elongation. That Pol II accumulates on many promoters in metazoans implies that steps other than Pol II recruitment are rate-limiting and regulated 1-6. By integrating genome-wide Pol II chromatin immunoprecipition (ChIP) and Global Run-On (GRO) genomic data sets from Drosophila cells, we examined critical features of Pol II near promoters. The accumulation of promoter-proximal polymerase is widespread, occurring on 70% of active genes; and unlike elongating Pol II within the body of genes, promoter Pol II are held paused by factors like NELF, unable to transcribe unless nuclei are treated with strong detergent. Notably, we find that the vast majority of promoter-proximal Pol II detected by ChIP are paused, thereby identifying the biochemical nature of this rate-limiting step in transcription. Finally, we demonstrate that Drosophila promoters do not have the upstream divergent Pol II that is seen so broadly and prominently on mammalian promoters. We postulate this is a consequence of Drosophila’s extensive use of directional core promoter sequence elements, which contrasts with mammals’ lack of directional elements and prevalence of CpG island core promoters. In support of this idea, we show that the fraction of mammalian promoters containing a TATA box core element is dramatically depleted of upstream divergent transcription.
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Project description:Identification of the Human DPR Promoter Element by using Machine Learning
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Project description:TATA box-containing promoters are often associated with tissue-specific effector genes, genes that are important for the structure and function of differentiated tissues. The underlying reason for this promoter preference is unclear, in part because tissue-specific genes have not been studied as widely as genes that drive embryonic development. To fill this gap in knowledge, we performed single-cell RNA-seq on differentiated cells derived from the late Drosophila embryo, identified the various tissues and analyzed the relationship between promoter types and gene expression across tissues. Our analysis confirmed the usage of TATA-containing promoters but revealed that tissue-specific effector genes are induced by two distinct promoter types, which have different mechanisms of regulation by RNA polymerase II (Pol II) and different expression characteristics. TATA-enriched promoters are highly tissue-specific and are only occupied by Pol II in the tissue in which they are active; the other promoter type is depleted in TATA motifs and shows high levels of paused Pol II throughout the embryo, even in tissues where the genes are not expressed. Interestingly, the single-cell RNA-seq data revealed that the paused promoters have more robust expression when expressed, but have higher background expression in tissues where these genes are not expressed. TATA genes, on the other hand, have little background expression, but larger variations in expression among the cells that show expression. To explain this difference, we propose that TATA-containing promoters have a higher activation barrier, but preferentially evolve in tissue-specific genes due to their strong activation potential and higher evolvability.
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Project description:TATA box-containing promoters are often associated with tissue-specific effector genes, genes that are important for the structure and function of differentiated tissues. The underlying reason for this promoter preference is unclear, in part because tissue-specific genes have not been studied as widely as genes that drive embryonic development. To fill this gap in knowledge, we performed single-cell RNA-seq on differentiated cells derived from the late Drosophila embryo, identified the various tissues and analyzed the relationship between promoter types and gene expression across tissues. Our analysis confirmed the usage of TATA-containing promoters but revealed that tissue-specific effector genes are induced by two distinct promoter types, which have different mechanisms of regulation by RNA polymerase II (Pol II) and different expression characteristics. TATA-enriched promoters are highly tissue-specific and are only occupied by Pol II in the tissue in which they are active; the other promoter type is depleted in TATA motifs and shows high levels of paused Pol II throughout the embryo, even in tissues where the genes are not expressed. Interestingly, the single-cell RNA-seq data revealed that the paused promoters have more robust expression when expressed, but have higher background expression in tissues where these genes are not expressed. TATA genes, on the other hand, have little background expression, but larger variations in expression among the cells that show expression. To explain this difference, we propose that TATA-containing promoters have a higher activation barrier, but preferentially evolve in tissue-specific genes due to their strong activation potential and higher evolvability.
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Project description:TATA box-containing promoters are often associated with tissue-specific effector genes, genes that are important for the structure and function of differentiated tissues. The underlying reason for this promoter preference is unclear, in part because tissue-specific genes have not been studied as widely as genes that drive embryonic development. To fill this gap in knowledge, we performed single-cell RNA-seq on differentiated cells derived from the late Drosophila embryo, identified the various tissues and analyzed the relationship between promoter types and gene expression across tissues. Our analysis confirmed the usage of TATA-containing promoters but revealed that tissue-specific effector genes are induced by two distinct promoter types, which have different mechanisms of regulation by RNA polymerase II (Pol II) and different expression characteristics. TATA-enriched promoters are highly tissue-specific and are only occupied by Pol II in the tissue in which they are active; the other promoter type is depleted in TATA motifs and shows high levels of paused Pol II throughout the embryo, even in tissues where the genes are not expressed. Interestingly, the single-cell RNA-seq data revealed that the paused promoters have more robust expression when expressed, but have higher background expression in tissues where these genes are not expressed. TATA genes, on the other hand, have little background expression, but larger variations in expression among the cells that show expression. To explain this difference, we propose that TATA-containing promoters have a higher activation barrier, but preferentially evolve in tissue-specific genes due to their strong activation potential and higher evolvability.
2021-01-25 | GSE120154 | GEO
Project description:TATA box-containing promoters are often associated with tissue-specific effector genes, genes that are important for the structure and function of differentiated tissues. The underlying reason for this promoter preference is unclear, in part because tissue-specific genes have not been studied as widely as genes that drive embryonic development. To fill this gap in knowledge, we performed single-cell RNA-seq on differentiated cells derived from the late Drosophila embryo, identified the various tissues and analyzed the relationship between promoter types and gene expression across tissues. Our analysis confirmed the usage of TATA-containing promoters but revealed that tissue-specific effector genes are induced by two distinct promoter types, which have different mechanisms of regulation by RNA polymerase II (Pol II) and different expression characteristics. TATA-enriched promoters are highly tissue-specific and are only occupied by Pol II in the tissue in which they are active; the other promoter type is depleted in TATA motifs and shows high levels of paused Pol II throughout the embryo, even in tissues where the genes are not expressed. Interestingly, the single-cell RNA-seq data revealed that the paused promoters have more robust expression when expressed, but have higher background expression in tissues where these genes are not expressed. TATA genes, on the other hand, have little background expression, but larger variations in expression among the cells that show expression. To explain this difference, we propose that TATA-containing promoters have a higher activation barrier, but preferentially evolve in tissue-specific genes due to their strong activation potential and higher evolvability.
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