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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 04, 2021 |
| Title |
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
A variety of self-interacting domains, defined at different levels of resolution, have been described in mammalian genomes. These include Chromatin Compartments (A and B), Topologically Associated Domains (TADs), contact domains, sub-TADs, insulated neighborhoods and frequently interacting regions (FIREs). Whereas many studies have found the organisation of self-interacting domains to be conserved across cell types, some do form in a lineage-specific manner. However, it is not clear to what degree such tissue-specific structures result from processes related to gene activity such as enhancer-promoter interactions or whether they form earlier during lineage commitment and are therefore likely to be prerequisite for promoting gene expression. To examine these models of genome organisation in detail, we used a combination of high-resolution chromosome conformation capture, a newly-developed form of quantitative fluorescence in-situ hybridisation and super-resolution imaging to study a 70 kb self-interacting domain containing the mouse alpha-globin locus. To understand how this self-interacting domain is established, we studied this structure when the genes are inactive and during erythroid differentiation when the genes are progressively switched on. In contrast to many current models of long-range gene regulation, we show that an erythroid-specific, decompacted self-interacting domain, delimited by convergent CTCF/cohesin binding sites, forms prior to the onset of robust gene expression. Using previously established mouse models we also show that formation of the self-interacting domain does not rely on interactions between the alpha-globin genes and their enhancers or on tissue-specific changes in CTCF binding. Rather, formation of the domain simply depends on the presence of activated lineage-specific cis-elements driving a transcription-independent mechanism for opening chromatin throughout the 70 kb region to create a permissive environment for gene expression. These findings are consistent with a model of loop-extrusion in which all segments of chromatin within a region delimited by CTCF boundary elements contact each other. Our findings suggest that activation of tissue-specific element(s) within such a self-interacting region is sufficient to influence all chromatin within such a domain.
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| Overall design |
NG Capture-C combines 3C library preparation with oligonucleotide capture for the desired viewpoint restriction fragments. Presented in this manuscript are chromosome11 viewpoints from promoters Hba1 and Hba2, enhancers R1 and R2 and CTCF binding site 39.5 in the alpha-globin subTAD, together with the central locations of plasmid FISH probes EX, E, A, C, CX designed at intervals across the locus. The method was applied to mES cells and to wild type mouse erythroblasts derived from in vitro culture of mouse foetal liver cells after 0h and 30h differentiation. We also derived erythroblasts from the foetal livers of a mouse model (AMKO) in which a 16kb region encompassing the entire Hba1 and Hba2 genes is deleted.
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| Contributor(s) |
Brown J, Roberts N, Oudelaar M, Telenius JM, Buckle V |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 04, 2017 |
| Last update date |
Apr 06, 2021 |
| 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 (2) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (39)
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| GSM2875617 |
Mouse Fetal liver cells (WT), Captured from: R1,R2 |
| GSM2875618 |
Mouse Fetal liver cells (AMKO), Captured from: R1, R2 |
| GSM2875619 |
Mouse embryonic stem cells, biol rep1, Captured from: R1, R2 |
| GSM2875620 |
Mouse embryonic stem cells, biol rep 2, Captured from: R1, R2 |
| GSM2875621 |
Mouse embryonic stem cells, biol rep 3, Captured from: R1, R2 |
| GSM2875622 |
Mouse Fetal liver cells, biol rep 1, Captured from: R1, R2 |
| GSM2875623 |
Mouse Fetal liver cells, biol rep 2, Captured from: R1, R2 |
| GSM2875624 |
Mouse Fetal liver cells, biol rep 3, Captured from: R1, R2 |
| GSM2875625 |
Mouse Fetal liver cells, NextSeq, 0 hour, biol rep 1, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875626 |
Mouse Fetal liver cells, NextSeq, 0 hour, biol rep 2, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875627 |
Mouse Fetal liver cells, NextSeq, 0 hour, biol rep 3, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875628 |
Mouse Fetal liver cells, NextSeq, 30 hours, biol rep 1, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875629 |
Mouse Fetal liver cells, NextSeq, 30 hours, biol rep 2, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875630 |
Mouse Fetal liver cells, NextSeq, 30 hours, biol rep 3, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875631 |
Mouse Fetal liver cells, MiSeq, 0 hour, biol rep1, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875632 |
Mouse Fetal liver cells, MiSeq, 0 hour, biol rep 2, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875633 |
Mouse Fetal liver cells, MiSeq, 0 hour, biol rep 3, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875634 |
Mouse Fetal liver cells, MiSeq, 30 hours, biol rep 1, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875635 |
Mouse Fetal liver cells, MiSeq, 30 hours, biol rep 2, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875636 |
Mouse Fetal liver cells, MiSeq, 30 hours, biol rep 3, Captured from: HS39.5, Hba-1, Hba-2 |
| GSM2875637 |
Mouse embryonic stem cells, biol rep 1, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875638 |
Mouse embryonic stem cells, biol rep 2, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875639 |
Mouse embryonic stem cells, biol rep 3, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875640 |
Mouse Fetal liver cells, biol rep 1, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875641 |
Mouse Fetal liver cells, biol rep 2, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875642 |
Mouse Fetal liver cells, biol rep 3, techn rep 1, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875643 |
Mouse embryonic stem cells, biol rep 3, techn rep 2, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875644 |
Mouse Fetal liver cells, biol rep 1, techn rep 2, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875645 |
Mouse Fetal liver cells, biol rep 2, techn rep 2, Captured from: FISH probes EX,E,A,C,CX |
| GSM2875646 |
Mouse Fetal liver cells, biol rep 3, techn rep 2, Captured from: FISH probes EX,E,A,C,CX |
| GSM3212680 |
Mouse fetal liver cells (KO), NextSeq, 30 hour, biol rep1 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212681 |
Mouse fetal liver cells (KO), NextSeq, 30 hour, biol rep2 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212682 |
Mouse fetal liver cells (KO), NextSeq, 30 hour, biol rep3 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212683 |
Mouse fetal liver cells (WT), NextSeq, 30 hour, biol rep1 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212684 |
Mouse fetal liver cells (WT), NextSeq, 30 hour, biol rep2 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212685 |
Mouse fetal liver cells (WT), NextSeq, 30 hour, biol rep3 Captured from: Hba1, Hba2 HS39.5 |
| GSM3212686 |
Mouse Fetal liver cells (WT), 30 hours, harvested prior to treatment |
| GSM3212687 |
Mouse Fetal liver cells (WT), 30 hours, treated with DMSO for 3 hours |
| GSM3212688 |
Mouse Fetal liver cells (WT), 30 hours, treated with DRB for 3 hours |
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| Relations |
| BioProject |
PRJNA421001 |
| SRA |
SRP126097 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107675_RAW.tar |
21.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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