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| Status |
Public on Apr 27, 2018 |
| Title |
Genetic dissection of the α-globin super-enhancer in vivo [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Mouse fetal liver erythroid RNA-seq. The RNA of the erythroid cells was metabolically labelled using 4-thiourdine nucleotide analogue supplementation of viable cells in culture. RNA transcripts that incorporated the analogue and hence were synthesised during this period of exposure, were then isolated from the pre-exiting bulk RNA by the addition of a biotin moiety and pull down.
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| Contributor(s) |
Hay D, Hughes JR, Telenius J, Higgs DR |
| Citation(s) |
27376235 |
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| Submission date |
Dec 22, 2017 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Jelena M Telenius |
| E-mail(s) |
jelena.telenius@ndcls.ox.ac.uk
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| Organization name |
Oxford University
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| Department |
Weatherall Institute of Molecular Medicine (WIMM)
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| Lab |
Genome Biology Research Group
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| Street address |
MRC Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Headington
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| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (1) |
| GSM2898780 |
Mouse wild type erythroid cells replicate 1 |
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| This SubSeries is part of SuperSeries: |
| GSE78835 |
Genetic dissection of the α-globin super-enhancer |
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| Relations |
| BioProject |
PRJNA427319 |
| SRA |
SRP127404 |
