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 and Ichiro Taniuchi ()
Additional contact information
Satoshi Kojo: RIKEN Center for Integrative Medical Sciences (IMS)
Hirokazu Tanaka: RIKEN Center for Integrative Medical Sciences (IMS)
Takaho A. Endo: RIKEN Center for Integrative Medical Sciences (IMS)
Sawako Muroi: RIKEN Center for Integrative Medical Sciences (IMS)
Ye Liu: RIKEN Center for Life Science Technologies (CLST)
Wooseok Seo: RIKEN Center for Integrative Medical Sciences (IMS)
Mari Tenno: RIKEN Center for Integrative Medical Sciences (IMS)
Kiyokazu Kakugawa: RIKEN Center for Integrative Medical Sciences (IMS)
Yoshinori Naoe: RIKEN Center for Integrative Medical Sciences (IMS)
Krutula Nair: RIKEN Center for Integrative Medical Sciences (IMS)
Kazuyo Moro: RIKEN Center for Integrative Medical Sciences (IMS)
Yoshinori Katsuragi: Niigata University
Akinori Kanai: Hiroshima University
Toshiya Inaba: Hiroshima University
Takeshi Egawa: Washington University School of Medicine
Byrappa Venkatesh: Technology and Research
Aki Minoda: RIKEN Center for Life Science Technologies (CLST)
Ryo Kominami: Niigata University
Ichiro Taniuchi: RIKEN Center for Integrative Medical Sciences (IMS)

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00768-1

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