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Status |
Public on Dec 09, 2022 |
Title |
A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification (Enhancer Reporter Sequencing) |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
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Overall design |
Targeted DNA sequencing of fragment libraries cloned into an enhancer reporter cassette in the HPRT locus of HM-1 ES cells and their differentiated progeny. Populations of cells were sorted for Venus-YFP reporter activity into negative, low, medium and high.
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Contributor(s) |
Edginton-White B, Maytum A, Kellaway SG, Goode DK, Keane P, Pagnuco I, Assi SA, Ames L, Clarke M, Cockerill PN, Göttgens B, Cazier J, Bonifer C |
Citation(s) |
36650172 |
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Submission date |
Mar 16, 2022 |
Last update date |
Feb 03, 2023 |
Contact name |
Peter Keane |
E-mail(s) |
p.keane@bham.ac.uk
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Organization name |
University of Birmingham
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Department |
Institute for Cancer and Genomic Sciences
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Street address |
Vincent Drive
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City |
Birmingham |
ZIP/Postal code |
B15 2TT |
Country |
United Kingdom |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (40)
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This SubSeries is part of SuperSeries: |
GSE198775 |
A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification |
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Relations |
BioProject |
PRJNA816848 |