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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_HaCaT] |
| Organism |
Homo sapiens |
| 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 ectopic IKAROS expression in HaCaT cells using a Tet-on strategy and performed HiChIPs for H3K27ac and CTCF at different time points to investigate the impact of IKAROS on regulatory and structural chromatin interactions in human skin epithelial cells which normally do not express IKAROS.
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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) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| GSM7305507 |
HaCaT_Tet-on-Luc, DoxD3, H3K27ac HiChIP |
| GSM7305508 |
HaCaT_Tet-on-Ikzf1, DoxD3, H3K27ac HiChIP |
| GSM7305509 |
HaCaT_Tet-on-Luc, DoxD3, CTCF HiChIP |
| GSM7305510 |
HaCaT_Tet-on-kzf1, DoxD3, CTCF HiChIP |
| GSM7305511 |
HaCaT_Tet-on-Ikzf1, DoxD3, IKAROS HiChIP, rep1 |
| GSM7305512 |
HaCaT_Tet-on-Ikzf1, DoxD3, IKAROS HiChIP, 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 |
PRJNA970045 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE231881_HiChIP_HaCat_Ik_Dox_D3_IKAROS.hic |
655.1 Mb |
(ftp)(http) |
HIC |
| GSE231881_RAW.tar |
2.5 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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