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

D Pham, CE Moseley, M Gao, D Savic, CJ Winstead… - Cell reports, 2019 - cell.com
D Pham, CE Moseley, M Gao, D Savic, CJ Winstead, M Sun, BL Kee, RM Myers, CT Weaver
Cell reports, 2019cell.com
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 …
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.
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