Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes

Satoshi Kojo, Hirokazu Tanaka, Takaho A. Endo, Sawako Muroi, Ye Liu, Wooseok Seo, Mari Tenno, Kiyokazu Kakugawa, Yoshinori Naoe, Krutula Nair, Kazuyo Moro, Yoshinori Katsuragi, Akinori Kanai, Toshiya Inaba, Takeshi Egawa, Byrappa Venkatesh, Aki Minoda, Ryo Kominami, Ichiro Taniuchi

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

T-lineage committed precursor thymocytes are screened by a fate-determination process mediated via T cell receptor (TCR) signals for differentiation into distinct lineages. However, it remains unclear whether any antecedent event is required to couple TCR signals with the transcriptional program governing lineage decisions. Here we show that Bcl11b, known as a T-lineage commitment factor, is essential for proper expression of ThPOK and Runx3, central regulators for the CD4-helper/CD8-cytotoxic lineage choice. Loss of Bcl11b results in random expression of these factors and, thereby, lineage scrambling that is disconnected from TCR restriction by MHC. Initial Thpok repression by Bcl11b prior to the pre-selection stage is independent of a known silencer for Thpok, and requires the last zinc-finger motif in Bcl11b protein, which by contrast is dispensable for T-lineage commitment. Collectively, our findings shed new light on the function of Bcl11b in priming lineage-specifying genes to integrate TCR signals into subsequent transcriptional regulatory mechanisms.

Original languageEnglish
Article number702
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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