GSE171610
Gene expression in mature CD4 and CD8 from WT mice and mature CD4 from DBTBLZ or Mta2-DBTBLZ retrogenic mice
T cell precursors develop into cytotoxic CD8 and helper CD4+ T cells in thymus. Thpok, a BTB/POZ family transcription factor, enforces commitment to the CD4 lineage and suppresses cytotoxic gene expression. However, it is still not fully understood how Thpok directs CD4 T cell development. Here, using mass-spectrometry, we identify nucleosome remodeling and deacetylase (NuRD) complex as a novel Thpok cofactor. We demonstrate that the Thpok BTB domain is essential for NuRD recruitment. Reconstituting NuRD binding to a BTB-less version of Thpok (which cannot bind NuRD) restored CD4 T cell in vivo. RNA sequencing showed that CD4 T cells expressing the reconstituted protein express a transcriptome similar to that of CD4 T cells expressing Thpok. Thus, our results demonstrate that NuRD recruitment is both necessary and sufficient for the function of the Thpok BTB domain in CD4 T cell development. Overall design: Bone marrows from Cd4-Cre+Thpokfl/fl mice transduced with retrovirus expressing DBTBLZ or Mta2-DBTBLZ were transplanted into irradiated recipient mice. Mature CD4 cells from host expressing DBTBLZ or Mta2-DBTBLZ were sorted. Mature CD4 cells and mature CD8 cells from C57BL/6 mice were also sorted as control. Gene expression was determined by RNA-seq.