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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719312616 |
| _version_ | 1818942220235964416 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Duy Pham |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-20T07:07:58Z |
| format | Article |
| id | doaj.art-5c538b770140414a9fd2816fdd9f10e0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T07:07:58Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5c538b770140414a9fd2816fdd9f10e02022-12-21T19:48:59ZengElsevierCell Reports2211-12472019-10-0129512031220.e7Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of CtcfDuy Pham0Carson E. Moseley1Min Gao2Daniel Savic3Colleen J. Winstead4Mengxi Sun5Barbara L. Kee6Richard M. Myers7Casey T. Weaver8Robin D. Hatton9Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USADepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USAInformatics Institute, University of Alabama at Birmingham, Birmingham, AL, USAHuman Genomics and Genetics, HudsonAlpha Institute for Biotechnology, Huntsville, AL, USADepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USADepartment of Pathology, The University of Chicago, Chicago, IL, USADepartment of Pathology, The University of Chicago, Chicago, IL, USAHuman Genomics and Genetics, HudsonAlpha Institute for Biotechnology, Huntsville, AL, USADepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding authorDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding authorSummary: 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 loopinghttp://www.sciencedirect.com/science/article/pii/S2211124719312616 |
| spellingShingle | 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 |
| title | Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf |
| title_full | Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf |
| title_fullStr | Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf |
| title_full_unstemmed | Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf |
| title_short | Batf Pioneers the Reorganization of Chromatin in Developing Effector T Cells via Ets1-Dependent Recruitment of Ctcf |
| title_sort | batf pioneers the reorganization of chromatin in developing effector t cells via ets1 dependent recruitment of ctcf |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719312616 |
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