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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE123209 | GEO | 2019/11/04

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC7182170 | biostudies-literature

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

Project description:We have examined mechanisms by which Batf acts to initiate gene transcription in developing effector CD4 T cells. We find that in addition to its pioneering function, Batf controls developmentally regulated recruitment of the chromatin architectural factor, Ctcf, to promote chromatin looping that is associated with transcription of lineage-specific genes. The chromatin organizing actions of Batf are largely Ets1-dependent, 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 Ap-1–Irf composite elements (AICEs), indicating that direct involvement of Batf-Irf complexes is not required. Thus, we have identified a cooperative role for Batf, Ets1 and Ctcf in chromatin reorganization that underpins transcriptional programming of effector T cells.

2019-11-04 | GSE123208 | GEO

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

2019-11-04 | GSE123206 | GEO

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

2019-11-04 | GSE123198 | GEO

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

Project description:Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf

| PRJNA507805 | ENA

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

Project description:Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [ATAC-seq]

| PRJNA507804 | ENA

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

Project description:Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [Hi-C]

| PRJNA507809 | ENA

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

Project description:Batf pioneers the reorganization of chromatin in developing effector T cells via Ets1-dependent recruitment of Ctcf [ChIP-seq]

| PRJNA507798 | ENA

Batf stabilizes Th17 cell development via impaired Stat5 recruitment of Ets1-Runx1 complexes.

Project description:Although the activator protein-1 (AP-1) factor Batf is required for Th17 cell development, its mechanisms of action to underpin the Th17 program are incompletely understood. Here, we find that Batf ensures Th17 cell identity in part by restricting alternative gene programs through its actions to restrain IL-2 expression and IL-2-induced Stat5 activation. This, in turn, limits Stat5-dependent recruitment of Ets1-Runx1 factors to Th1- and Treg-cell-specific gene loci. Thus, in addition to pioneering regulatory elements in Th17-specific loci, Batf acts indirectly to inhibit the assembly of a Stat5-Ets1-Runx1 complex that enhances the transcription of Th1- and Treg-cell-specific genes. These findings unveil an important role for Stat5-Ets1-Runx1 interactions in transcriptional networks that define alternate T cell fates and indicate that Batf plays an indispensable role in both inducing and maintaining the Th17 program through its actions to regulate the competing actions of Stat5-assembled enhanceosomes that promote Th1- and Treg-cell developmental programs.

| S-EPMC10106990 | biostudies-literature

Batf Stabilizes Th17 Cell Development via Impaired Stat5 Recruitment of Ets1-Runx1 Complexes

Project description:Although the activator protein-1 (AP-1) factor Batf is required for Th17 cell development, its mechanisms of action to underpin the Th17 program are incompletely understood. Here we find that Batf ensures Th17 cell identity in part by restricting alternative gene programs through its actions to restrain IL-2 expression and IL-2-induced Stat5 activation. This, in turn, limits Stat5-dependent recruitment of Ets1-Runx1 factors to Th1 and Treg cell-specific gene loci. Thus, in addition to pioneering regulatory elements in Th17-specific loci, Batf acts indirectly to inhibit assembly of a Stat5-Ets1-Runx1 complex that enhances transcription of Th1 and Treg cell-specific genes. These findings unveil an important role for Stat5-Ets1-Runx1 interactions in transcriptional networks that define alternate T cell fates and indicate that Batf plays an indispensable role in both inducing and maintaining the Th17 program through its actions to regulate the competing actions of Stat5-assembled enhanceosomes that promote Th1 and Treg-cell developmental programs.

| S-SCDT-10_15252-EMBJ_2021109803 | biostudies-other

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