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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 [HiChIP_LpreB_Inducible] |
| Organism |
Mus musculus |
| Experiment type |
Other
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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 induced IkE5 deletion in established large pre-B cell culture and performed HiChIPs for H3K27ac, SMC1a and CTCF at different time points to investigate the temporal change in regulatory and structural interactions upon IkE5 deletion.
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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 07, 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 (9)
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| GSM7305498 |
Large preB_inducible IkE5 deletion, DMSO control, H3K27ac HiChIP, rep1 |
| GSM7305499 |
Large preB_inducible IkE5 deletion, 4OHT induction day3, H3K27ac HiChIP, rep1 |
| GSM7305500 |
Large preB_inducible IkE5 deletion, 4OHT induction day12, H3K27ac HiChIP, rep1 |
| GSM7305501 |
Large preB_inducible IkE5 deletion, DMSO control, H3K27ac HiChIP, rep2 |
| GSM7305502 |
Large preB_inducible IkE5 deletion, 4OHT induction day3, H3K27ac HiChIP, rep2 |
| GSM7305503 |
Large preB_inducible IkE5 deletion, 4OHT induction day12, H3K27ac HiChIP, rep2 |
| GSM7305504 |
Large preB_inducible IkE5 deletion, DMSO control, CTCF HiChIP, replicate 1 |
| GSM7305505 |
Large preB_inducible IkE5 deletion, 4OHT induction day3, CTCF HiChIP, rep1 |
| GSM7305506 |
Large preB_inducible IkE5 deletion, 4OHT induction day12, CTCF HiChIP, rep1 |
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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 |
PRJNA970040 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE231880_RAW.tar |
10.0 Gb |
(http)(custom) |
TAR (of HIC) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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