Transient promoter interactions modulate developmental gene activation [CaptureC]
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ABSTRACT:
PROVIDER: PRJNA1085198 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional induction coincides with the formation of various chromatin topologies, including loss and gain of physical interactions between promoters and distal regulatory elements (DREs). Strong evidence supports that gene activation is accompanied by a general increase in promoter-enhancer interactions. However, it remains unclear how these topological changes are coordinated across time and space to collectively enable transcription. Here we combine chromatin conformation capture with profiling of histone modifications, RNA polymerase II and transcription during an embryonic stem cell differentiation time-course to determine how 3D genome restructuring is related to transcriptional transitions. Using this approach, our data identifies distinct topological alterations that are associated with the magnitude of transcriptional induction. We detect transiently formed interactions between gene promoters and DREs and demonstrate by genetic deletions that these DREs can contribute to the transcriptional induction of associated genes. Finally, by acutely depleting cohesin, we interfere with early transient promoter-enhancer interactions, and show that this impairs the activation of linked genes. Taken together, our study identifies typical topological alterations during gene activation, links them to the magnitude of transcriptional induction, and detects an uncharacterized type of transcriptional enhancers. Our data are compatible with a model where the type of topological pattern that a promoter displays during developmental transitions and the dynamics and magnitude of its transcriptional induction are interdependent.
2024-10-29 | GSE261064 | GEO
Project description:Transient promoter interactions modulate developmental gene activation [ChIPseq]
| PRJNA1084859 | ENA
Project description:Transient promoter interactions modulate developmental gene activation [RNA-Seq]
| PRJNA1085204 | ENA
Project description:Transcriptional induction coincides with the formation of various chromatin topologies, including loss and gain of physical interactions between promoters and distal regulatory elements (DREs). Strong evidence supports that gene activation is accompanied by a general increase in promoter-enhancer interactions. However, it remains unclear how these topological changes are coordinated across time and space to collectively enable transcription. Here we combine chromatin conformation capture with profiling of histone modifications, RNA polymerase II and transcription during an embryonic stem cell differentiation time-course to determine how 3D genome restructuring is related to transcriptional transitions. Using this approach, our data identifies distinct topological alterations that are associated with the magnitude of transcriptional induction. We detect transiently formed interactions between gene promoters and DREs and demonstrate by genetic deletions that these DREs can contribute to the transcriptional induction of associated genes. Finally, by acutely depleting cohesin, we interfere with early transient promoter-enhancer interactions, and show that this impairs the activation of linked genes. Taken together, our study identifies typical topological alterations during gene activation, links them to the magnitude of transcriptional induction, and detects an uncharacterized type of transcriptional enhancers. Our data are compatible with a model where the type of topological pattern that a promoter displays during developmental transitions and the dynamics and magnitude of its transcriptional induction are interdependent.
2024-10-29 | GSE261039 | GEO
Project description:Transcriptional induction coincides with the formation of various chromatin topologies, including loss and gain of physical interactions between promoters and enhancers. While strong evidence supports that gene activation is accompanied by a general increase in promoter-enhancer interactions, how these topological changes are coordinated across time and space with other types of interactions to collectively enable gene activation remains unresolved. Here we combine chromatin conformation capture with the profiling of histone modifications and transcription during a finely resolved time-course of embryonic stem cell differentiation to determine how genome restructuring in 3D correlates with and informs transcriptional transitions. Our data indicates that genome restructuring follows only a few common patterns that are related to the magnitude of transcriptional induction. Using this approach we identify transiently formed interactions between gene promoters and distal regulatory elements for which we demonstrate by genetic deletion that they can contribute to the transcriptional induction of associated genes. Finally, using acute depletion of cohesin, we prevent the formation of early promoter-enhancer interactions, and show that this impairs the activation of corresponding genes, compatible with the possibility that early topological changes are instructive for transcription. Taken together, our study identifies the variety of typical topological changes during gene activation, detects an uncharacterized type of transcriptional enhancers and provides evidence that the earliest topological changes can affect the magnitude of gene activation. Our data agrees with the idea that the multitude of topological changes account for appropriate gene induction during cell differentiation.
2024-10-29 | GSE261066 | GEO
Project description:CDK-Mediator and FBXL19 cooperate in the induction of developmental genes by promoting regulatory interactions [CaptureC]
| PRJNA562667 | ENA
Project description:Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here, we investigate the 3D conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. 61% of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer–promoter and enhancer–enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer–promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general significance of enhancer–promoter physical proximity for developmental gene activation in mammals.
2024-01-03 | GSE217078 | GEO
Project description:Promoter R-loops Recruit U2AF1 to Modulate Its Phase Separation and RNA Splicing
| PRJNA958138 | ENA
Project description:Appropriate developmental gene regulation relies on the capacity of gene promoters to integrate inputs from distal regulatory elements, yet how this is achieved remains poorly understood. In embryonic stem cells (ESCs), a subset of silent developmental gene promoters are primed for activation by FBXL19, a CpG island binding protein, through its capacity to recruit CDK-Mediator. How mechanistically these proteins function together to prime genes for activation during differentiation is unknown. Here we discover that in mouse ESCs FBXL19 and CDK-Mediator support long-range interactions between silent gene promoters that rely on FBXL19 for their induction during differentiation and gene regulatory elements. During gene induction, these distal regulatory elements behave in an atypical manner, in that the majority do not acquire histone H3 lysine 27 acetylation and no longer interact with their target gene promoter following gene activation. Despite these atypical features, we demonstrate by targeted deletions that these distal elements are required for appropriate gene induction during differentiation. Together these discoveries demonstrate that CpG-island associated gene promoters can prime genes for activation by communicating with atypical distal gene regulatory elements to achieve appropriate gene expression.
2020-01-21 | GSE136423 | GEO
Project description:Alteration of genome folding via engineered transposon insertion [CaptureC]
| PRJNA565260 | ENA