Genomics

Dataset Information

0

Early B Cell Factor 4 modulates FAS-mediated apoptosis and promotes cytotoxic function in human immune cells [ATAC-seq]


ABSTRACT: Apoptosis is a genetically regulated program of cell death that plays a key role in immune disease processes. We identified EBF4, a little-studied member of the early B cell factor (EBF) family of transcription factors, in a whole-genome CRISPR screen for regulators of Fas/APO-1/CD95-mediated T cell death. Loss of EBF4 increases the half-life of the c-FLIP protein and its presence in the Fas signaling complex impairs caspase-8 cleavage and apoptosis. Transcriptome analysis revealed that EBF4 regulates molecules such as TBX21, EOMES, granzyme, and perforin that are important for human natural killer (NK) and CD8+ T cell functions. Bio-ID - mass spectrometry analyses showed EBF4 binding to STAT3, STAT5, and MAP kinase 3, and a strong pathway relationship to IL-2 regulated genes which are known to govern cytotoxicity pathways. ChIP-seq analysis defined a canonical EBF4 binding motif 5’-CCCNNGG/AG-3’ closely related to the EBF1 binding site and using a luciferase-based reporter, we found a dose-dependent transcriptional response of this motif to EBF4. We also conducted ATAC-seq in EBF4 overexpressing cells and found increased chromatin accessibility upstream of granzyme and perforin and in topologically associated domains in human lymphocytes. Finally, we discovered that the EBF4 has basal expression in human but not mouse NK cells and CD8+ T cells and vanishes following activating stimulation. Together our data reveal key features of a previously unknown transcriptional regulator of human cytotoxic immune function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206220 | GEO | 2022/07/27

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-07-27 | GSE206219 | GEO
2022-07-27 | GSE206221 | GEO
2021-09-09 | PXD018982 | Pride
2021-05-01 | GSE150342 | GEO
2019-03-16 | GSE128392 | GEO
2009-01-13 | E-GEOD-13727 | biostudies-arrayexpress
2017-08-23 | GSE92710 | GEO
2017-08-23 | GSE92709 | GEO
2008-12-04 | GSE13727 | GEO
2008-12-04 | GSE13726 | GEO