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| Status |
Public on Feb 03, 2022 |
| Title |
Differential Regulation of Transcription Factor T-bet Induction during NK Cell Development and Th1 Cell Differentiation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Adaptive CD4 T helper cells and their innate counterparts, innate lymphoid cells, utilize an identical set of lineage-determining transcription factors (LDTFs) for their differentiation and functions. However, the similarities and differences in the induction of the LDTFs in these lymphocytes are still elusive. Here we show that type 1 T helper (Th1) cells and natural killer (NK) cells displayed distinct epigenomes at the Tbx21 locus, which encodes T-bet, the LDTF for type 1 lymphocytes. The initial induction of T-bet in NK precursors was partially dependent on the NK-specific DNase I hypersensitive site Tbx21-CNS-3 and the expression of IL-18 receptor; IL-18 induced T-bet expression through RUNX3, which binds to Tbx21-CNS-3. By contrast, Tbx21-CNS-12 containing STAT binding motifs was critical for IL-12-induced T-bet expression during Th1 cell differentiation both in vitro and in vivo. Thus, innate and adaptive lymphocytes of same class may utilize distinct enhancer elements for their development and differentiation.
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| Overall design |
Naïve CD4 T cells were isolated from lymph node and cultured under Th1, Th2, or Th17 condition for DNase-seq or ChIP-seq using anti-T-bet antibodies. cNK cells and ILC1s were isolated from liver for DNase-seq. cNK cells were isolated from spleen for ChIP-seq using anti-T-bet antibodies. ILC2s and LTi cells were isolated from small intestine for DNase-seq.
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| Contributor(s) |
Fang D, Cui K, Cao Y, Zheng M, Kawabe T, Hu G, Khillan JS, Li D, Zhong C, Jankovic D, Sher A, Zhao K, Zhu J |
| Citation(s) |
35381213 |
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| Submission date |
Apr 19, 2021 |
| Last update date |
May 05, 2022 |
| Contact name |
Yaqiang Cao |
| E-mail(s) |
caoyaqiang0410@gmail.com
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| Organization name |
NHLBI
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| Department |
System Biology Center
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| Lab |
Laboratory of Epigenome Biology
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA723025 |
| SRA |
SRP315389 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE172358_RAW.tar |
6.3 Gb |
(http)(custom) |
TAR (of BED, BEDPE, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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