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Super-enhancers require enhancers and facilitators to fully activate gene expression

ABSTRACT: Super-enhancers require enhancers and facilitators to fully activate gene expression

PROVIDER: PRJNA909802 | ENA |

REPOSITORIES: ENA

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Super-enhancers require enhancers and facilitators to fully activate gene expression [ChIP-seq]

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Project description:Super-enhancers are compound regulatory elements which control expression of key cell-identity genes. They recruit high levels of tissue-specific transcription factors, co-activators such as the mediator complex, and they contact their target gene promoters with high frequency. Most super-enhancers contain multiple constituent regulatory elements, but it is unclear whether these elements have distinct roles in activating expression of their cognate genes. Here, through comprehensively rebuilding the endogenous α-globin super-enhancer, we show that super-enhancers comprise bioinformatically equivalent but functionally distinct element types: classical enhancers and facilitator elements. Facilitators have no intrinsic enhancer activity, yet in their absence, classical enhancers are unable to fully up-regulate their target genes. Without facilitators, classical enhancers exhibit reduced mediator recruitment, enhancer RNA transcription and enhancer-promoter interactions. Facilitators are interchangeable, but display functional hierarchy based on their position within a super-enhancer. Facilitators thus play an important role in potentiating super-enhancer activity and ensuring robust activation of target genes.

2023-12-31 | GSE219077 | GEO

Super-enhancers require enhancers and facilitators to fully activate gene expression [RNA-seq]

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Super-enhancers require enhancers and facilitators to fully activate gene expression [ChIP-seq]

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Super-enhancers require enhancers and facilitators to fully activate gene expression [ATAC-seq]

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Super-enhancers require enhancers and facilitators to fully activate gene expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-31 | GSE220463 | GEO

Super-enhancers include classical enhancers and facilitators to fully activate gene expression.

Project description:Super-enhancers are compound regulatory elements that control expression of key cell identity genes. They recruit high levels of tissue-specific transcription factors and co-activators such as the Mediator complex and contact target gene promoters with high frequency. Most super-enhancers contain multiple constituent regulatory elements, but it is unclear whether these elements have distinct roles in activating target gene expression. Here, by rebuilding the endogenous multipartite α-globin super-enhancer, we show that it contains bioinformatically equivalent but functionally distinct element types: classical enhancers and facilitator elements. Facilitators have no intrinsic enhancer activity, yet in their absence, classical enhancers are unable to fully upregulate their target genes. Without facilitators, classical enhancers exhibit reduced Mediator recruitment, enhancer RNA transcription, and enhancer-promoter interactions. Facilitators are interchangeable but display functional hierarchy based on their position within a multipartite enhancer. Facilitators thus play an important role in potentiating the activity of classical enhancers and ensuring robust activation of target genes.

| S-EPMC10858684 | biostudies-literature

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