Identification of active gene regulatory elements in the human and murine TBX3 locus
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ABSTRACT:
PROVIDER: PRJNA606524 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11080200_1.fastq.gz | Fastqsanger.gz | |||
| SRR11080200_2.fastq.gz | Fastqsanger.gz | |||
| SRR11080201_1.fastq.gz | Fastqsanger.gz | |||
| SRR11080201_2.fastq.gz | Fastqsanger.gz | |||
| SRR11080202_1.fastq.gz | Fastqsanger.gz |
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Project description:The human and murine TBX3 locus harbors hundreds of active regulatory elements responding to Smad-/Gata- and Tcf-transcription factors in vitro.
2020-07-20 | GSE145257 | GEO
Project description:Rationale: The atrioventricular conduction system controls ventricular activation and is delineated by expression of Tbx3. Genome-wide association studies identified genetic variants near TBX3 associated with conduction velocities (PR interval and QRS duration), suggesting minor changes in TBX3 dose affect conduction system function. Objective: To assess whether and how Tbx3 dose reduction affects the integrity of the atrioventricular conduction system. Methods and Results: Electrocardiograms revealed a PR interval shortening and prolonged QT interval and QRS duration in heterozygous Tbx3 mutants compared to wild-types. We observed that the atrioventricular bundle and proximal bundle branches of Tbx3+/- mice after birth became hypoplastic, whereas the size of the atrioventricular node was not affected. The transcriptomes of wild-type and Tbx3+/- atrioventricular nodes were analyzed using BAC-Tbx3-Egfp mice enabling specific isolation of the atrioventricular node by laser capture microdissection followed by RNA-sequencing. Hundreds of genes were slightly but consistently deregulated. Cross-referencing with transcriptome data of isolated cardiomyocytes of the conduction system and chamber myocardium derived from Tbx3+/Venus;BAC-Nppb-Katushka hearts revealed that a set of chamber-enriched genes, including Kcne1 (MinK), Ryr2, and Scn5a, were upregulated in Tbx3+/- atrioventricular nodes, whereas conduction system-enriched genes, including Hcn4 and Cacna2d2, were downregulated. We performed ATAC-sequencing on purified fetal Tbx3+ atrioventricular cardiomyocytes to identify potential atrioventricular-specific regulatory DNA elements on a genome-wide scale, and identified regulatory elements mediating the Tbx3-dependent regulation of Ryr2 and other target genes in the atrioventricular node. Conclusions: Tbx3 dose reduction results in deregulation of a large number of genes affecting the electrical properties of the atrioventricular node and causes failure to maintain the structural integrity of the atrioventricular bundle. These data provide a mechanism underlying differences in PR interval and QRS duration in individuals carrying associated variants in the TBX3 locus.
2019-10-18 | GSE121464 | GEO
Project description:Rationale: The atrioventricular conduction system controls ventricular activation and is delineated by expression of Tbx3. Genome-wide association studies identified genetic variants near TBX3 associated with conduction velocities (PR interval and QRS duration), suggesting minor changes in TBX3 dose affect conduction system function. Objective: To assess whether and how Tbx3 dose reduction affects the integrity of the atrioventricular conduction system. Methods and Results: Electrocardiograms revealed a PR interval shortening and prolonged QT interval and QRS duration in heterozygous Tbx3 mutants compared to wild-types. We observed that the atrioventricular bundle and proximal bundle branches of Tbx3+/- mice after birth became hypoplastic, whereas the size of the atrioventricular node was not affected. The transcriptomes of wild-type and Tbx3+/- atrioventricular nodes were analyzed using BAC-Tbx3-Egfp mice enabling specific isolation of the atrioventricular node by laser capture microdissection followed by RNA-sequencing. Hundreds of genes were slightly but consistently deregulated. Cross-referencing with transcriptome data of isolated cardiomyocytes of the conduction system and chamber myocardium derived from Tbx3+/Venus;BAC-Nppb-Katushka hearts revealed that a set of chamber-enriched genes, including Kcne1 (MinK), Ryr2, and Scn5a, were upregulated in Tbx3+/- atrioventricular nodes, whereas conduction system-enriched genes, including Hcn4 and Cacna2d2, were downregulated. We performed ATAC-sequencing on purified fetal Tbx3+ atrioventricular cardiomyocytes to identify potential atrioventricular-specific regulatory DNA elements on a genome-wide scale, and identified regulatory elements mediating the Tbx3-dependent regulation of Ryr2 and other target genes in the atrioventricular node. Conclusions: Tbx3 dose reduction results in deregulation of a large number of genes affecting the electrical properties of the atrioventricular node and causes failure to maintain the structural integrity of the atrioventricular bundle. These data provide a mechanism underlying differences in PR interval and QRS duration in individuals carrying associated variants in the TBX3 locus.
2019-10-18 | GSE121244 | GEO
Project description:Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Five genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands and account for 50% of mRNAs during lactation, two (Prr27, Fdcsp) are salivary-specific and one (Odam) has dual specificity. We probed the function of 12 candidate control elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitated the 10,000-fold activation of Csn2 during pregnancy. Our work identifies regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements.
2023-07-28 | GSE231439 | GEO
Project description:Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Five genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands and account for 50% of mRNAs during lactation, two (Prr27, Fdcsp) are salivary-specific and one (Odam) has dual specificity. We probed the function of 12 candidate control elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitated the 10,000-fold activation of Csn2 during pregnancy. Our work identifies regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements.
2023-07-28 | GSE231438 | GEO
Project description:Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Five genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands and account for 50% of mRNAs during lactation, two (Prr27, Fdcsp) are salivary-specific and one (Odam) has dual specificity. We probed the function of 12 candidate control elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitated the 10,000-fold activation of Csn2 during pregnancy. Our work identifies regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements.
2023-07-28 | GSE231440 | GEO
Project description:ChIP-seq is combined with RNA-seq analysis to identify the TBX3 and HAND2 target genes during mouse limb bud development. This analysis identifies the DEGs and direct transcriptional targets of HAND2 and TBX3 during the early determinative period critical to establishment of limb axis polarity and the SHH signaling center in the posterior limb bud mesenchyme. In particular, bioinformatics analysis identifies the target gene networks that are co-regulated by both TBX3 and HAND2 transcription factors in the limb bud mesenchyme. A significant fraction of the target genes identified are required for normal limb bud development and their spatio-temporal expression patterns are changed in mutant limb buds at early stages. This project was supported by SNSF Grant 310030_184734 to Rolf Zeller (project partner: Aimée Zuniga).
2023-12-31 | GSE192485 | GEO
Project description:ChIP-seq is combined with RNA-seq analysis to identify the TBX3 and HAND2 target genes during mouse limb bud development. This analysis identifies the DEGs and direct transcriptional targets of HAND2 and TBX3 during the early determinative period critical to establishment of limb axis polarity and the SHH signaling center in the posterior limb bud mesenchyme. In particular, bioinformatics analysis identifies the target gene networks that are co-regulated by both TBX3 and HAND2 transcription factors in the limb bud mesenchyme. A significant fraction of the target genes identified are required for normal limb bud development and their spatio-temporal expression patterns are changed in mutant limb buds at early stages. This project was supported by SNSF Grant 310030_184734 to Rolf Zeller (project partner: Aimée Zuniga).
2023-12-31 | GSE192484 | GEO
Project description:The purposes of this study were to compare and analyze the expression differences of mouse papillary thyroid carcinoma (mPTC) induced by BrafV600E after Tbx3 deletion. And in order to gain insights into global gene expression regulated by TBX3 in human PTC cells, RNA-Seq experiments were performed in K1 cells with knockdown of TBX3.
2021-04-30 | GSE166513 | GEO
Project description:Cell-specific and shared regulatory elements control a multi-gene locus active in mammary and salivary glands
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