Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [Hi-C]

We have examined mechanisms by which Batf acts to initiate gene transcription in developing effector CD4 T cells. We find that in addition to its pioneering function, Batf controls developmentally regulated recruitment of the chromatin architectural factor, Ctcf, to promote chromatin looping that is associated with transcription of lineage-specific genes. The chromatin organizing actions of Batf are largely Ets1-dependent, which appears to be indispensable for the Batf-dependent recruitment of Ctcf. Moreover, most of the Batf-dependent sites to which Ctcf is recruited lie outside of Ap-1–Irf composite elements (AICEs), indicating that direct involvement of Batf-Irf complexes is not required. Thus, we have identified a cooperative role for Batf, Ets1 and Ctcf in chromatin reorganization that underpins transcriptional programming of effector T cells. Overall design: Naïve CD4+ T cells isolated from spleen/lymph nodes were activated with anti-CD3 and anti-CD28 with or without IL-6 for 96 h. D4 activated WT and BatfKO cells with or without IL-6.