| Autor: |
Kueh HY; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Yui MA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Ng KK; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Pease SS; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Zhang JA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Damle SS; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Freedman G; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Siu S; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA., Bernstein ID; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Elowitz MB; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA., Rothenberg EV; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA. |
| Abstrakt: |
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. |
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