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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 14, 2019 |
| Title |
The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells [MBD-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
The transcriptional repression of alternative lineage genes is critical for cell fate commitment. Mechanisms by which locus-specific gene silencing is initiated and heritably maintained during cell division are not clearly understood. To study the maintenance of silent gene states, we investigated how the Cd4 gene is stably repressed in CD8+ T cells. Through CRISPR and shRNA screening, we identified the histone chaperone CAF-1 as a critical component for Cd4 repression. We found that the large subunit of CAF-1, Chaf1a, requires the N-terminal KER domain to associate with the histone deacetylases HDAC1/2 and the histone demethylase LSD1, enzymes that also participate in Cd4 silencing. When CAF-1 was lacking, Cd4 derepression was markedly enhanced in the absence of the de novo DNA methyltransferase Dnmt3a, but not the maintenance DNA methyltransferase Dnmt1. In contrast to Dnmt1, Dnmt3a deficiency did not significantly alter levels of DNA methylation at the Cd4 locus. Instead, Dnmt3a deficiency sensitized CD8+ T cells to Cd4 derepression mediated by compromised functions of histone modifying factors, including the enzymes associated with CAF-1. Thus, we propose that the heritable silencing of the Cd4 gene in CD8+ T cells exploits cooperative functions among the DNA methyltransferases, CAF-1, and histone modifying enzymes.
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| Overall design |
There are 3 samples total consisting of Cas9Tg CD8+ T cells electroporated with sgRNA. Control sgRNA (Olfr2) CD8+CD4- T cells, Dnmt1 sgRNA treated CD8+CD4+ and Dnmt3a sgRNA treated CD8+CD4+ T cells were processed for genome-wide DNA methylation analysis as described in the methods.
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| Contributor(s) |
Ng C, Aichinger M, Nguyen T, Au C, Najar T, Wu L, Mesa KR, Will L, Quivy J, Benjamin H, Almouzni G, Zuber J, Littman DR |
| Citation(s) |
30975723 |
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| Submission date |
Mar 13, 2019 |
| Last update date |
May 15, 2019 |
| Contact name |
Dan Littman |
| E-mail(s) |
Dan.Littman@nyumc.org
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| Phone |
212-263-7520
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| Organization name |
NYU School of Medicine
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| Street address |
430 E 29th St Acls-West Tower 4th Fl Room 460E
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| City |
new york |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE126472 |
The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells |
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| Relations |
| BioProject |
PRJNA526880 |
| SRA |
SRP188344 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128245_RAW.tar |
929.4 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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