Zfp281 and Zfp148 control CD4+ T cell thymic development and Th2 functions. (ChIP-seq)

How CD4+-lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by Th2 effector cells. Genetic, single-cell, and spatial transcriptomic analyses show that these factors promote the intrathymic CD4+ T cell differentiation of MHC II-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promote chromatin opening at and expression of Th2 cytokine genes, but not of the Th2 lineage determining transcription factor Gata3. Zfp281 interacts with Gata3, and binds Gata3 genomic binding sites at loci encoding Thpok and Th2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and Th2 cell responses. Overall design: CD4+ T cells were activated with IL-4, anti-IFNg, and anti-IL12 (Th2 conditions) for 5 days, then processed for ChIP-Seq.