Runx factors launch T cell and innate lymphoid programs via direct and gene network-based mechanisms
-
1.
California Institute of Technology
Abstract
Runx factors are essential for lineage specification of various hematopoietic cells, including T lymphocytes. However, they regulate context-specific genes and occupy distinct genomic regions in different cell types. Here, we show that dynamic Runx binding shifts in early T-cell development are mostly not restricted by local chromatin state but regulated by Runx dosage and functional partners. Runx co-factors compete to recruit a limited pool of Runx factors in early T-progenitors, and a modest increase in Runx protein availability at pre-commitment stages causes premature Runx occupancy at post-commitment binding sites. This results in striking T-lineage developmental acceleration by selectively activating T-identity and innate lymphoid cell programs. These are collectively regulated by Runx together with other, Runx-induced transcription factors that co-occupy Runx target genes and propagate gene network changes.
Copyright and License
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Acknowledgement
We thank Rothenberg lab members for helpful discussions, Rochelle Diamond and members of the Caltech Flow Cytometry and Cell Sorting facility for sorting, Igor Antoshechkin and Vijaya Kumar of the Caltech Jacobs Genomics Facility for bulk RNA sequencing, Henry Amrhein and Diane Trout for computer support, Jeff Park and Sisi Chen from the Caltech Single Cell Profiling and Engineering Center for providing support for processing 10X Chromium samples, Ingrid Soto for mouse care, Maria Quiloan for mouse genotyping and supervision.
Attached Files
Submitted - 2022.11.18.517146v1.full.pdf
Supplemental Material - media-1.pdf
Supplemental Material - media-2.csv
Supplemental Material - media-3.csv
Supplemental Material - media-4.csv
Supplemental Material - media-5.xlsx
Supplemental Material - media-6.xlsx
Files
| Name | Size | Download all |
|---|---|---|
|
md5:1577f8d5da8c748f47a2970c04df0cb5
|
20.2 MB | Preview Download |
|
md5:e19e4c4c63dd795883d3721608856889
|
1.4 MB | Preview Download |
|
md5:b0c37b255311d338cf398d4b686d33a1
|
3.1 MB | Download |
|
md5:6a89ad4386bba914dea8b1f87bbe60f9
|
21.1 kB | Download |
|
md5:eb71edc49f0e4ed9ae6b95fb9fcd41fb
|
12.0 MB | Preview Download |
|
md5:44aa41c7718b5a5b8e5b709f940b313e
|
75.3 kB | Preview Download |
|
md5:958c39a353d70316f33b393b3a8d3c76
|
29.0 kB | Preview Download |
Additional details
- California Institute of Technology
- Caltech groups
- Division of Biology and Biological Engineering, Millard and Muriel Jacobs Genetics and Genomics Laboratory
- Publication Status
- Submitted