Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf

Abstract

Summary: The basic leucine zipper transcription factor activating transcription factor-like (Batf) contributes to transcriptional programming of multiple effector T cells and is required for T helper 17 (Th17) and T follicular helper (Tfh) cell development. Here, we examine mechanisms by which Batf initiates gene transcription in developing effector CD4 T cells. We find that, in addition to its pioneering function, Batf controls developmentally regulated recruitment of the architectural factor Ctcf to promote chromatin looping that is associated with lineage-specific gene transcription. The chromatin-organizing actions of Batf are largely dependent on Ets1, 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 activating protein-1-interferon regulatory factor (Ap-1-Irf) composite elements (AICEs), indicating that direct involvement of Batf-Irf complexes is not required. These results identify a cooperative role for Batf, Ets1, and Ctcf in chromatin reorganization that underpins the transcriptional programming of effector T cells. : Pham et al. uncover mechanisms by which Batf restructures the chromatin landscape during CD4+ effector T cell differentiation. Batf controls Ctcf recruitment to lineage-specifying gene loci in an Ets1-dependent manner to promote chromatin looping and lineage-specific gene transcription, thereby identifying a heretofore unknown cooperativity of these factors in effector T cell development. Keywords: CD4 T cell differentiation, Batf, Ets1, Ctcf, chromatin accessibility, chromatin looping