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

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...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2019-10-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719312616
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Summary: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
ISSN:2211-1247