PT  - JOURNAL ARTICLE
AU  - Shin, Boyoung
AU  - Zhou, Wen
AU  - Wang, Jue
AU  - Gao, Fan
AU  - Rothenberg, Ellen V.
TI  - Runx factors launch T-cell and innate lymphoid programs via direct and gene network-based mechanisms
AID  - 10.1101/2022.11.18.517146
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.18.517146
4099  - http://biorxiv.org/content/early/2022/11/19/2022.11.18.517146.short
4100  - http://biorxiv.org/content/early/2022/11/19/2022.11.18.517146.full
AB  - 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.Competing Interest StatementThere is potential Competing Interest. Dr. Rothenberg is a member of the Scientific Advisory Board for Century Therapeutics, and has consulted for Kite Pharma and A2 Biotherapeutics.