Genetic dissection of the α-globin super-enhancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA314091 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3198740_1.fastq.gz | Fastqsanger.gz | |||
| SRR3198740_2.fastq.gz | Fastqsanger.gz | |||
| SRR3198750_1.fastq.gz | Fastqsanger.gz | |||
| SRR3198750_2.fastq.gz | Fastqsanger.gz | |||
| SRR3199670_1.fastq.gz | Fastqsanger.gz |
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Project description:Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. These super-enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the α-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation, without clear evidence of synergistic or higher-order effects. Our study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation.
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Project description:Many genes determining cell identity are regulated by a set of enhancer elements collectively referred to as super-enhancers. It has been suggested that super-enhancers represent a new class of cis-element, in which the assembly of enhancers confers an emergent property from the extended regulatory domain. To investigate this, we used published criteria to define one of the strongest super-enhancers in mouse erythroid cells – a 24kb region regulating α-globin expression, which comprises five enhancer-like components. Using homologous recombination, we deleted each component of this super-enhancer, singly and in informative combinations, and examined hematologic phenotype, gene expression, chromatin structure and chromosome conformation. Each component behaves independently, in an additive rather than synergistic manner. We conclude that the sub-classification of enhancers is unjustified beyond a description of their strength, which is defined by the number of lineage-specific transcription factors they bind. These findings ask afresh why enhancer-like elements cluster at key genes.
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