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

Duy Pham, Carson E Moseley, Min Gao, Daniel Savic, Colleen J Winstead, Mengxi Sun, Barbara L Kee, Richard M Myers, Casey T Weaver, Robin D Hatton

Cell reports 2019 Oct 29

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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. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Duy Pham, Carson E Moseley, Min Gao, Daniel Savic, Colleen J Winstead, Mengxi Sun, Barbara L Kee, Richard M Myers, Casey T Weaver, Robin D Hatton. Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf. Cell reports. 2019 Oct 29;29(5):1203-1220.e7