A Bidirectional Non-Coding RNA Promoter Mediates Long-Range Gene Expression Regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE264638 | GEO | 2024/05/26
REPOSITORIES: GEO
Similar Datasets
Project description:Recent evidence suggests that human gene promoters display gene expression regulatory mechanisms beyond the typical single gene local transcription modulation. In mammalian genomes, genes with an associated bidirectional promoter are abundant; bidirectional promoter architecture serves as a regulatory hub for a gene pair expression. However, it has been suggested that its contribution to transcriptional regulation might exceed local transcription initiation modulation. Despite their abundance, the functional consequences of bidirectional promoter architecture remain largely unexplored. This work studies the long-range gene expression regulatory role of a long-non-coding RNA gene promoter using chromosome conformation capture methods. We found that this particular bidirectional promoter contributes to distal gene expression regulation in a target-specific manner by establishing promoter-promoter interactions. In particular, we validated that bidirectional promoter is contacting multiple gene promoter elements, including BBX promoter, upon loss-of-function assays reduced bidirectional-promoter interactions associated with increased BBX promoter-enhancer and augmented gene expression. Moreover, long-range regulatory functionality is not directly dependent on its associated non-coding gene pair expression levels.
2024-05-26 | GSE264663 | GEO
Project description:Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid Trypanosoma brucei. Our analyses revealed that the predicted histone methyltransferase SET27 and the Chromodomain protein CRD1 are tightly concentrated at RNAPII transcription start regions (TSRs). Here we report that SET27 and CRD1, together with four previously uncharacterized constituents, form the SET27 promoter-associated regulatory complex (SPARC), which is specifically enriched at TSRs. SET27 loss leads to aberrant RNAPII recruitment to promoter sites, accumulation of polyadenylated transcripts upstream of normal transcription start sites, and conversion of some normally unidirectional promoters to bidirectional promoters. Transcriptome analysis in the absence of SET27 revealed upregulated mRNA expression in the vicinity of SPARC peaks within the main body of chromosomes in addition to derepression of genes encoding variant surface glycoproteins (VSGs) located in subtelomeric regions. These analyses uncover a novel chromatin-associated complex required to establish accurate promoter position and directionality.
2023-03-11 | PXD036454 | Pride
Project description:Long-range interactions between DNA regulatory elements and their target genes play major roles in gene regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary haematopoietic cell types. We show that long-range promoter interactions are highly cell-type specific, preferentially linking active promoters and enhancers. Patterns of promoter interactions reflect cell lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched for expression quantitative trait loci with effects on their interacting target genes. We exploit this rich resource of interactome maps to connect non-coding disease variants to their target promoters, identifying thousands of new disease-candidate genes, and implicating a number of gene pathways in disease susceptibility. Our results demonstrate the power of promoter interactomes from primary cells to reveal insights into genomic regulatory mechanisms underlying common diseases.
| EGAS00001001911 | EGA
Project description:Although DNA motifs recognized by the transcription factors (TFs) have been determined, challenges remain in probing in vivo architecture of TF-DNA complexes on a genome-wide scale. Here, we show in vivo architecture of Escherichia coli arginine repressor (ArgR)-DNA complexes using chromatin immunoprecipitation coupled with sequencing (ChIP-exo). The identified 62 ArgR-binding loci were classified into three groups, comprised of single, double, and triple peak-pairs, respectively. Each peak-pair has unique 93 bp-long (±2 bp) ArgR-binding sequence containing two ARG boxes (39 bp) and residual sequence. Moreover, the peak-pairs provided the three ArgR-binding modes defined by the position of the two ARG boxes, indicating that the formation of DNA bending apparently centered between the pair of ARG boxes facilitates the non-specific contacts between ArgR subunits and the residual sequences. Thus, our data postulate the in vivo architecture of ArgR-DNA complexes to understand its transcription regulatory mechanism. ChIP-exo profiles of ArgR (+Arginine) and ArgR (-Arginine) were generated by deep sequencing in duplicates using Illumina MiSeq.
2015-04-01 | E-GEOD-60546 | biostudies-arrayexpress
Project description:Although DNA motifs recognized by the transcription factors (TFs) have been determined, challenges remain in probing in vivo architecture of TF-DNA complexes on a genome-wide scale. Here, we show in vivo architecture of Escherichia coli arginine repressor (ArgR)-DNA complexes using chromatin immunoprecipitation coupled with sequencing (ChIP-exo). The identified 62 ArgR-binding loci were classified into three groups, comprised of single, double, and triple peak-pairs, respectively. Each peak-pair has unique 93 bp-long (±2 bp) ArgR-binding sequence containing two ARG boxes (39 bp) and residual sequence. Moreover, the peak-pairs provided the three ArgR-binding modes defined by the position of the two ARG boxes, indicating that the formation of DNA bending apparently centered between the pair of ARG boxes facilitates the non-specific contacts between ArgR subunits and the residual sequences. Thus, our data postulate the in vivo architecture of ArgR-DNA complexes to understand its transcription regulatory mechanism.
2015-04-01 | GSE60546 | GEO
Project description:<p>In order to evaluate whether rare regulatory variants in the vicinity of promoters are likely to impact gene expression, we conducted a novel burden test for rare variants at the extreme of expression. After targeted sequencing of 2kb promoter regions of 472 genes in 410 healthy adults, burden tests were performed by calculating the summed rare allele counts in ranked expression level bins using Illumina whole blood microarray gene expression data. The results clearly show an enrichment of rare variants at both extremes of gene expression. The rare regulatory variant effects were also partitioned into subsets of genes based on their regulatory functions, positions relative to transcription start sites, disease relatedness, with some intriguing biases. The enrichment of rare regulatory variants in extremely expressed genes was replicated in an independent sample of 75 individuals with RNASeq and whole genome sequence information. Participants were from the Emory-Georgia Tech Center for Health Discovery and Well Being (CHDWB) longitudinal cohort study, but only baseline gene expression data was used.</p>
| phs001021 | dbGaP
Project description:Robust regulatory architecture of pan-neuronal gene expression
| PRJNA779059 | ENA
Project description:Rantasalo2015-Synthetic_expresion_modulator_constitutiveSTF_VP16
This model is part of a family of models describing a modular synthetic expression system that modulates the expression level of a gene in S. Cerevisae. The whole family of models is described in the article:
Synthetic transcription amplifier system for orthogonal control of gene expression in Saccharomyces cerevisiae, by
Anssi Rantasalo, Elena Czeizler, Riitta Virtanen, Juho Rousu, Harri Lähdesmäki, Merja Penttilä, Jussi Jäntti and Dominik Mojzita (submitted).
The family comprises 5 different models corresponding to the synthetic systems using:
1) the methionine induced synthetic transcription factor sTF-VP16 construct,
2) the methionine induced synthetic transcription factor sTF-B42 construct,
3) the constitutive sTF-VP16 construct,
4) the constitutive sTF-B42 construct, and
5) the constitutive sTF-VP16 construct with a different core promoter for the reporter gene.
The computational models were designed, developed and implemented by Elena Czeizler, Harri Lahdesmaki and Juho Rousu and they are all hosted separately in the Biomodels database.
The only difference between the models corresponding to the constitutive and the methionine-induced systems stands in the sTF transcription process. The only difference between the models for the systems using the sTF16 or sTF42 constructs stands in the kinetic rates associated to 2 reactions: i) the association of the polymerase with the sTF’s bound to their specific DNA sites and ii) the degradation rate of the sTF proteins corresponding to the two transcription factors sTF16 or sTF42. The first 4 models correspond to systems using the pBID2-EP core promoter for the reporter mCherry gene. Starting from the model associated to the constitutive system using the sTF16 construct we derived the 5th model corresponding to the case when the core promoter for the reporter mCherry gene is switched from pBID2-EP to pBID2-ED. The only difference between these two last models stands in the kinetic rates for the association of polymerase bound to sTF and the core promoter.
Since the 5 considered models have many parts in common, the values for the kinetic parameters corresponding to these common parts are identical in all of them.
The current model describes the gene expression modulation system using the constitutive synthetic transcription factor sTF-VP16 composed of a LexA DNA binding domain, the Herpes simplex virus transactivation domain (VP16) and a 6×His-tag. In this model, the number of boxes to which this sTF can bind (encoded in the species B) is set to 2. In the experimental setups, the number of binding boxes varied between 0 and 16 (8 binding sites on each of the 2 DNA constructs), which can be easily modified in the model by changing the initial value for B. The core promoter used for the reporter mCherry gene is pBID-EP.
All model analysis and simulations were done by using the software COPASI (Hoops, S., Sahle, S., Gauges, R., Lee, C., Pahle, J., Simus, N., Singhal, M., Xu, L., Mendes, P. and Kummer, U. (2006) COPASI- A COmplex PAthway SImulator. Bioinformatics, 22, 3067-3074.)
2016-02-23 | MODEL1510230001 | BioModels
Project description:Rantasalo2015-Synthetic_expresion_modulator_constitutiveSTF_VP16_pBID2-EDcorePromoter
This model is part of a family of models describing a modular synthetic expression system that modulates the expression level of a gene in S. Cerevisae. The whole family of models is described in the article:
Synthetic transcription amplifier system for orthogonal control of gene expression in Saccharomyces cerevisiae, by
Anssi Rantasalo, Elena Czeizler, Riitta Virtanen, Juho Rousu, Harri Lähdesmäki, Merja Penttilä, Jussi Jäntti and Dominik Mojzita (submitted).
The family comprises 5 different models corresponding to the synthetic systems using:
1) the methionine induced synthetic transcription factor sTF-VP16 construct,
2) the methionine induced synthetic transcription factor sTF-B42 construct,
3) the constitutive sTF-VP16 construct,
4) the constitutive sTF-B42 construct, and
5) the constitutive sTF-VP16 construct with a different core promoter for the reporter gene.
The computational models were designed, developed and implemented by Elena Czeizler, Harri Lahdesmaki and Juho Rousu and they are all hosted separately in the Biomodels database.
The only difference between the models corresponding to the constitutive and the methionine-induced systems stands in the sTF transcription process. The only difference between the models for the systems using the sTF16 or sTF42 constructs stands in the kinetic rates associated to 2 reactions: i) the association of the polymerase with the sTF’s bound to their specific DNA sites and ii) the degradation rate of the sTF proteins corresponding to the two transcription factors sTF16 or sTF42. The first 4 models correspond to systems using the pBID2-EP core promoter for the reporter mCherry gene. Starting from the model associated to the constitutive system using the sTF16 construct we derived the 5th model corresponding to the case when the core promoter for the reporter mCherry gene is switched from pBID2-EP to pBID2-ED. The only difference between these two last models stands in the kinetic rates for the association of polymerase bound to sTF and the core promoter.
Since the 5 considered models have many parts in common, the values for the kinetic parameters corresponding to these common parts are identical in all of them.
The current model describes the gene expression modulation system using the constitutive synthetic transcription factor sTF-VP16 composed of a LexA DNA binding domain, the Herpes simplex virus transactivation domain (VP16) and a 6×His-tag. In this model, the number of boxes to which this sTF can bind (encoded in the species B) is set to 2. In the experimental setups, the number of binding boxes varied between 0 and 16 (8 binding sites on each of the 2 DNA constructs), which can be easily modified in the model by changing the initial value for B. The core promoter used for the reporter mCherry gene is pBID2-ED.
All model analysis and simulations were done by using the software COPASI (Hoops, S., Sahle, S., Gauges, R., Lee, C., Pahle, J., Simus, N., Singhal, M., Xu, L., Mendes, P. and Kummer, U. (2006) COPASI- A COmplex PAthway SImulator. Bioinformatics, 22, 3067-3074.)
2016-02-23 | MODEL1510230003 | BioModels
Project description:Rantasalo2015-Synthetic_expresion_modulator_constitutiveSTF_B42
This model is part of a family of models describing a modular synthetic expression system that modulates the expression level of a gene in S. Cerevisae. The whole family of models is described in the article:
Synthetic transcription amplifier system for orthogonal control of gene expression in Saccharomyces cerevisiae, by
Anssi Rantasalo, Elena Czeizler, Riitta Virtanen, Juho Rousu, Harri Lähdesmäki, Merja Penttilä, Jussi Jäntti and Dominik Mojzita (submitted).
The family comprises 5 different models corresponding to the synthetic systems using:
1) the methionine induced synthetic transcription factor sTF-VP16 construct,
2) the methionine induced synthetic transcription factor sTF-B42 construct,
3) the constitutive sTF-VP16 construct,
4) the constitutive sTF-B42 construct, and
5) the constitutive sTF-VP16 construct with a different core promoter for the reporter gene.
All 5 computational models were developed by Elena Czeizler and Harri Lahdesmaki and they are all hosted separately in the Biomodels database.
The only difference between the models corresponding to the constitutive and the methionine-induced systems stands in the sTF transcription process. The only difference between the models for the systems using the sTF16 or sTF42 constructs stands in the kinetic rates associated to 2 reactions: i) the association of the polymerase with the sTF’s bound to their specific DNA sites and ii) the degradation rate of the sTF proteins corresponding to the two transcription factors sTF16 or sTF42. The first 4 models correspond to systems using the pBID2-EP core promoter for the reporter mCherry gene. Starting from the model associated to the constitutive system using the sTF16 construct we derived the 5th model corresponding to the case when the core promoter for the reporter mCherry gene is switched from pBID2-EP to pBID2-ED. The only difference between these two last models stands in the kinetic rates for the association of polymerase bound to sTF and the core promoter.
Since the 5 considered models have many parts in common, the values for the kinetic parameters corresponding to these common parts are identical in all of them.
The current model describes the gene expression modulation system using the constitutive synthetic transcription factor sTF-B42 composed of a LexA DNA binding domain, the SV40 nuclear localization signal and the B42 activation domain. In this model, the number of boxes to which this sTF can bind (encoded in the species B) is set to 2. In the experimental setups, the number of binding boxes varied between 0 and 16 (8 binding sites on each of the 2 DNA constructs), which can be easily modified in the model by changing the initial value for B. The core promoter used for the reporter mCherry gene is pBID-EP.
All model analysis and simulations were done by using the software COPASI (Hoops, S., Sahle, S., Gauges, R., Lee, C., Pahle, J., Simus, N., Singhal, M., Xu, L., Mendes, P. and Kummer, U. (2006) COPASI- A COmplex PAthway SImulator. Bioinformatics, 22, 3067-3074.)
2016-02-23 | MODEL1510230002 | BioModels