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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 HaCaT] |
| Organism |
Homo sapiens |
| 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 RNA-seq in HaCaT keratinocyte cells. Doxycycline (Dox) was added into the culture medium to a final concentration of 0.1μg/ml to induce the expression of IKAROS (HaCaT_Tet-on_Ik1) or Luciferase (HaCaT_Tet-on_Luc).
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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 09, 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) |
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| Samples (10)
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| GSM7310821 |
HaCaT_Tet-on-Ikzf1, Dox+, Day3, rep1 |
| GSM7310822 |
HaCaT_Tet-on-Luc, Dox-, rep2 |
| GSM7310823 |
HaCaT_Tet-on-Ikzf1, Dox+, Day1, rep2 |
| GSM7310824 |
HaCaT_Tet-on-Ikzf1, Dox+, Day2, rep2 |
| GSM7310825 |
HaCaT_Tet-on-Ikzf1, Dox+, Day3, rep2 |
| GSM7310826 |
HaCaT_Tet-on-Luc, Dox+, Day3, rep1 |
| GSM7310827 |
HaCaT_Tet-on-Luc, Dox+, Day3, 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 |
PRJNA970699 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232041_Hacat_Ik_Luc_Induction.noadj.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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