| First Author | Kueh HY | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 8 | Pages | 956-65 |
| PubMed ID | 27376470 | Mgi Jnum | J:260615 |
| Mgi Id | MGI:6142650 | Doi | 10.1038/ni.3514 |
| Citation | Kueh HY, et al. (2016) Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment. Nat Immunol 17(8):956-65 |
| abstractText | During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus ''poising'' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation. |
