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Series GSE136538 Query DataSets for GSE136538
Status Public on Oct 30, 2019
Title Transcription factor Tox2 functions to promote chromatin remodeling during T follicular helper (Tfh) cell development (ATAC-seq)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary T Follicular helper (Tfh) cell is an effector CD4+ T cell subset specialized in helping B cells in germinal centers (GC) reactions. Although Bcl6 was identified as a Tfh-specific transcription factor essential for their development, the molecular mechanisms underlying Bcl6 regulation and Tfh cell commitment remain unclear. Here, we report that Tox2 transcription factor is highly expressed in Tfh cells, regulated by Bcl6 and STAT3. Forced expression of Tox2 drives Bcl6 expression and Tfh development. Mechanistically, Tox2 directly binds to Tfh-associated genes, including Bcl6, and functions to promote their chromatin accessibility and modulate the activities of other Tfh-regulating factors. Conversely, genetic deletion of Tox2 results in defective Tfh differentiation, and inhibiting both Tox and Tox2 in T cells abolishes Tfh differentiation and GC response. Thus, our results demonstrate that Tox2 is a key transcription factor that regulates Bcl6 expression and Tfh development and suggest a Tox2-Bcl6 axis in feed-forward regulation of Tfh program.
 
Overall design The in vivo-generated CD4+CD44hiCXCR5hiBcl6-RFPhiFoxp3-GFP- Tfh cells sorted from Bcl6-RFPFoxp3-GFP mice immunized with KLH/CFA and the T cells activated in vitro under indicated conditions were harvest for ATAC-seq analysis.
 
Contributor(s) Xu W, Zhao X
Citation(s) 31732165
Submission date Aug 28, 2019
Last update date Dec 04, 2019
Contact name Chen Dong
Organization name Tsinghua University
Department Institute for Immunology and School of Medicine
Lab Dongchen's lab
Street address Haidian District
City Beijing
ZIP/Postal code 100084
Country China
 
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (8)
GSM4051209 CD4+ T cells: CM - ATACseq
GSM4051210 CD4+ T cells: Th0 (GFP) - ATACseq
GSM4051211 CD4+ T cells: Th0 (Tox2) - ATACseq
Relations
BioProject PRJNA562636
SRA SRP219586

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE136538_RAW.tar 835.5 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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