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Series GSE107675 Query DataSets for GSE107675
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
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.
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.
Contributor(s) Brown J, Roberts N, Oudelaar M, Telenius JM, Buckle V
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Submission date Dec 04, 2017
Last update date Apr 06, 2021
Contact name Jelena M Telenius
Organization name Oxford University
Department Weatherall Institute of Molecular Medicine (WIMM)
Lab Genome Biology Research Group
Street address MRC Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Headington
City Oxford
ZIP/Postal code OX3 9DS
Country United Kingdom
Platforms (2)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (39)
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
BioProject PRJNA421001
SRA SRP126097

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Supplementary file Size Download File type/resource
GSE107675_RAW.tar 21.8 Mb (http)(custom) TAR (of TXT)
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Processed data provided as supplementary file
Raw data are available in SRA

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