Transcriptional Regulation by NFATc1 during murine thymocyte development [ChIP-seq]

In thymus hematopoietic precursor cells differentiate into αβ T cells, γδ T cells, mucosa-associated invariant T cells (MAIT), and natural killer T (NKT) cells. We show that both ablation of NFATc1 or its induction during the DN stages of thymocyte development leads to an almost normal thymocyte development but a marked increase in γδ T cells. The γδ cells deficient for NFATc1 acquire an NKT γδ cell phenotype that exhibits the expression of CD4 co-receptor, the NK1.1 marker, the augmented usage of the Vγ1.1 and Vδ6.3 segments, and an increased in IL4 and IFN-γ production. DNA binding of NFATc1A in murine thymocytes (either directly ex vivo (-) or in vitro stimulated by TPA and ionomycin for 4 hours(+)) analyzed by ChIP and deep sequencing. Cells from genotype Rosa26BirA expressing BirA ligase only are used as control. Cells from genotype Nfatc1/A-Bio.Rosa26BirA express an modified NFATc1A protein from a BAC transgene that is biotinylated by BirA in vivo.