Chromatin structures in pre-selection DP thymocytes of WT and Bcl11b hypomorphic mutant

T-cell receptor (TCR) signals play a critical role in guiding selected thymocytes to distinct lineages by activating genes for transcription factors, such as ThPOK and Runx3, for the helper- or cytotoxic-lineage, respectively. Here we show that Bcl11b, known as an early T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3. Loss of Bcl11b resulted in premature and random expression of these specification factors, leading to lineage scrambling that was disconnected from TCR restriction by MHC. Early Thpok repression by Bcl11b is independent of its known transcriptional silencer, but requires the C-terminal zinc-finger of Bcl11b. Collectively, our findings shed new light on the role of Bcl11b in priming lineage-specifying genes to integrate TCR signals into a subsequent developmental program that dissects effector lineages. Sequencing of ATAC-seq from pre-selection DP thymocytes.