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| Status |
Public on Nov 20, 2023 |
| Title |
A multiscale 3D chromatin architecture that controls development of the humoral immune system is assembled by IKAROS [RNA-Seq 3] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A generic level of chromatin organization generated by the interplay between cohesin and CTCF suffices to limit promiscuous interactions between regulatory elements, but a lineage-specific assembly of chromatin that supercedes these constraints is required to configure the genome to support the gene expression changes that guide faithful lineage progression. Using loss-of-function approaches in B cell precursors in vivo we show that IKAROS assembles interactions between sites often separated by megabase distances to configure a significant fraction of the genome in preparation for lymphoid development. Interactions emanating from IKAROS-bound enhancers override CTCF-imposed boundaries and assemble lineage-specific regulatory units built on a backbone of smaller invariant topological domains.In vitro deletion provides temporal resolution to changes in chromatin modifications, loops, and compartmental localization. Gain-of-function experiments in epithelial cells confirm IKAROS’ ability to reconfigure chromatin architecture at multiple scales. While the compaction of the Igk locus required for genome editing represents a function of IKAROS unique to the lymphoid system, the more general function of this lineage-defining DNA binding protein to preconfigure the genome to support lineage specific gene expression and suppress activation of extra-lineage genes provides a paradigm for lineage restriction.
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| Overall design |
We performed in situ Hi-C in wild-type and IkE5Δ/Δ large pre-B cells to understand IKAROS’ function in the genome organization in early B cell development.
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| Contributor(s) |
Hu Y, Salgado Figueroa D, Zhang Z, Vaselits M, Bhattacharyya S, Clark MR, Kashiwagi M, Morgan BA, Ay F, Georgopoulos K |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 18, 2023 |
| Last update date |
Nov 20, 2023 |
| Contact name |
Katia Georgopoulos |
| E-mail(s) |
katia.georgopoulos@cbrc2.mgh.harvard.edu
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| Phone |
617-7264445
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| Organization name |
Harvard Medical School
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| Department |
CBRC
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| Lab |
Georgopoulos
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| Street address |
1st and 13th St
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| City |
Charlestown |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM7646199 |
splenic B1a cell, WT, rep2 |
| GSM7646200 |
splenic marginal zone B cell, WT, rep 1 |
| GSM7646201 |
splenic marginal zone B cell, WT, rep 2 |
| GSM7646202 |
splenic folliculaar B cell, WT, rep1 |
| GSM7646203 |
splenic folliculaar B cell, WT, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE232490 |
A multiscale 3D chromatin architecture that controls development of the humoral immune system is assembled by IKAROS |
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| Relations |
| BioProject |
PRJNA996298 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237725_WT_SplenicBcellsDeseq2SimpleNorm.txt.gz |
973.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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