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GEO help: Mouse over screen elements for information. |
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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 [ChIP-seq LpreB cell] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy 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 |
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications and transcription factors in wildtype and IkE5Δ/Δ large preB cells
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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 |
May 12, 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 (2) |
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| Samples (41)
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| GSM7336792 |
Large preB cell, IKDN, CTCF, rep2 |
| GSM7336793 |
Large preB cell, WT, SMC1A, rep1 |
| GSM7336794 |
Large preB cell, IKDN, SMC1A, rep1 |
| GSM7336795 |
Large preB cell, WT, SMC1A, rep2 |
| GSM7336796 |
Large preB cell, IKDN, SMC1A, rep2 |
| GSM7336797 |
Large preB cell, WT, IKAROS, rep1 |
| GSM7336798 |
Large preB cell, WT, IKAROS, rep2 |
| GSM7336799 |
Large preB cell, WT, H3K4me3, rep1 |
| GSM7336800 |
Large preB cell, IKDN, H3K4me3, rep1 |
| GSM7336801 |
Large preB cell, WT, H3K4me3, rep2 |
| GSM7336802 |
Large preB cell, IKDN, H3K4me3, rep2 |
| GSM7336803 |
Large preB cell, WT, IL7 withdrawal day2, H3K4me3, rep1 |
| GSM7336804 |
Large preB cell, WT, IL7 withdrawal day2 H3K4me3, rep2 |
| GSM7336805 |
Large preB cell, WT, H3K27ac, rep1 |
| GSM7336806 |
Large preB cell, IKDN, H3K27ac,rep1 |
| GSM7336807 |
Large preB cell, WT, H3K27ac, rep2 |
| GSM7336808 |
Large preB cell, IKDN, H3K27ac,rep2 |
| GSM7336809 |
Large preB cell, WT, H3K4me1 |
| GSM7336810 |
Large preB cell, IKDN, H3K4me1 |
| GSM7336811 |
Large preB cell, WT, H3K36me3 |
| GSM7336812 |
Large preB cell, IKDN, H3K36me3 |
| GSM7336813 |
Large preB cell, WT, Input |
| GSM7336814 |
Large preB cell, IKDN, Input |
| GSM7336815 |
Large preB cell, inducible IkE5 deletion, DMSO/Induction D0, H3K27ac, rep1 |
| GSM7336816 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D3, H3K27ac, rep1 |
| GSM7336817 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D12, H3K27ac, rep1 |
| GSM7336818 |
Large preB cell, inducible IkE5 deletion, DMSO/Induction D0, H3K27ac, rep2 |
| GSM7336819 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D3, H3K27ac, rep2 |
| GSM7336820 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D12, H3K27ac, rep2 |
| GSM7336821 |
Large preB cell, inducible IkE5 deletion, DMSO/Induction D0, CTCF, rep1 |
| GSM7336822 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D3, CTCF, rep1 |
| GSM7336823 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D12, CTCF, rep1 |
| GSM7336824 |
Large preB cell, inducible IkE5 deletion, DMSO/Induction D0, CTCF, rep2 |
| GSM7336825 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D3, CTCF, rep2 |
| GSM7336826 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D12, CTCF, rep2 |
| GSM7336827 |
Large preB cell, inducible IkE5 deletion, DMSO/Induction D0, input |
| GSM7336828 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D3, Input |
| GSM7336829 |
Large preB cell, inducible IkE5 deletion, 4OHT induction D12, Input |
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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 |
PRJNA972129 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232463_RAW.tar |
8.1 Gb |
(http)(custom) |
TAR (of BEDGRAPH, BW, TBI) |
| GSE232463_WTLpreB_IKAROS_R1_R2.pileup.bedgraph.gz |
388.5 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE232463_WTLpreB_IKAROS_R1_R2.pileup.bedgraph.gz.tbi.gz |
541.4 Kb |
(ftp)(http) |
TBI |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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