Transcriptional drivers of the T-cell lineage program

The T-cell development program is specifically triggered by Notch-Delta signaling, but most transcription factors needed to establish T-cell lineage identity also have crossover roles in other hematopoietic lineages. This factor sharing complicates full definition of the core gene regulatory circuits required for T-cell specification. But new advances illuminate the roles of three of the most T-cell specific transcription factors. Commitment to the T-cell lineage is now shown to depend on Bcl11b, while initiation of the T-cell differentiation program begins earlier with the induction of TCF-1 (Tcf7 gene product) and GATA-3. Several reports now reveal how TCF-1 and GATA-3 are mobilized in early T cells and the pathways for their T-lineage specific effects.

► Notch, TCF-1, GATA-3, and Bcl11b are linked in a T-cell gene network.
► Bcl11b is needed for commitment but not to initiate the T-cell program.
► GATA-3 action is regulated via transcription, translation, and binding site selection.
► TCF-1 (Tcf7) is a direct Notch target required from the Early T-cell Precursor stage.
► TCF-1 can bypass the requirement for Notch itself to activate Gata3 and Bcl11b.