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| Status |
Public on Jul 12, 2016 |
| Title |
UTX controls lineage-specific epigenetic program of iNKT cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
NKT cells are innate-like lymphocytes that protect against infection, autoimmune disease, and cancer. However, little is known about epigenetic regulation of iNKT cell development. Here, we show that the H3K27me3 histone demethylase UTX is an essential cell-intrinsic factor that controls an iNKT lineage specific gene expression program and epigenetic landscape in a demethylase activity dependent manner. UTX-deficient iNKT cells exhibit impaired expression of iNKT signature genes due to a decrease in activation-associated H3K4me3 and an increase in repressive H3K27me3 marks within the promoters that UTX occupies. Notably, we identified JunB as a novel regulator of iNKT development that partners with UTX to establish an iNKT lineage specific gene expression program. Moreover, we demonstrate that UTX-mediated regulation of super-enhancer accessibility is a key mechanism for iNKT lineage commitment. These findings uncover how UTX regulates iNKT cell development through multiple epigenetic mechanisms.
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| Overall design |
Chromatin profiles of Wild type and UTX-KO iNKT cells were generated by ChIP-seq and ATAC-seq using Illumina platform.
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| Contributor(s) |
Beyaz S, Pinello L |
| Citation(s) |
27992400 |
| |
| Submission date |
Jul 11, 2016 |
| Last update date |
Nov 14, 2020 |
| Contact name |
Luca Pinello |
| Organization name |
Dana-Farber Cancer Institute
|
| Street address |
450 brookline avenue
|
| City |
boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA328452 |
| SRA |
SRP078241 |
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