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| Status |
Public on Dec 22, 2021 |
| Title |
Batf-mediated Epigenetic Control of Effector CD8+ T Cell Differentiation (HiChIP) |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
The response of naive CD8+ T cells to their cognate antigen involves rapid and broad changes in gene expression that are coupled with extensive chromatin remodeling, but the mechanisms governing these changes are not fully understood. In this study, we investigated how this process depends on the activity of the basic leucine zipper ATF-like transcription factor Batf, which is essential for the earliest phase of effector CD8+ T cell differentiation. Through genome scale profiling of multiple modalities, we characterized the role of Batf in chromatin organization at several levels, including the accessibility of key regulatory regions, the expression of nearby genes, and the interactions these regions make with each other and with key transcription factors. We quantified the dependencies between Batf and other transcription factors and identified a core transcription factor network that cooperated with Batf, including Irf4, and the transcription factors Runx3 and T-bet, which tended to co-localize with Batf and bind in regions whose accessibility and long-range interactions were mediated by Batf. We functionally demonstrated the synergistic activity of this network in initiating aspects of the effector T cells’ transcriptional and chromatin accessibility profiles in an ectopically-induced fibroblast system. Using HiChIP, we further found that overexpressing all four factors in fibroblasts was required to recapitulate important aspects of the CD8+ T cell chromatin architecture. Our results provided a comprehensive resource for studying the epigenomic and transcriptomic landscape of effector differentiation of cytotoxic T cells and suggested various modes of dependencies between transcription factors in this process.
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| Overall design |
This submission contains the HiChIP portion of the data. P14 CD8+ T Cells and NIH/3T3 fibroblasts ectopically expressing Batf, Batf/Irf4, and Batf/Irf4/Runx3/T-bet were subjected to HiChIP for Batf. Additional samples were subjected to HiChIP for Ctcf.
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| Contributor(s) |
Tsao H, Kaminski J |
| Citation(s) |
35179948 |
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| Submission date |
Dec 21, 2021 |
| Last update date |
Mar 23, 2022 |
| Contact name |
Jim Kaminski |
| E-mail(s) |
[email protected]
|
| Organization name |
Boston Children's Hospital
|
| Street address |
1 Blackfan Circle
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE192390 |
Batf-mediated Epigenetic Control of Effector CD8+ T Cell Differentiation |
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| Relations |
| BioProject |
PRJNA791329 |
| SRA |
SRP351941 |
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