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Series GSE126471 Query DataSets for GSE126471
Status Public on Feb 13, 2019
Title The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells (ATACseq II)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
Overall design There are 12 samples total. There are 10 samples consisting of sorted CD8+ T cells with or without expression of CD4 after knock-down with shRNAs targeting Dnmt1 or Chaf1a. There are 2 samples consisting of sorted CD8+ T cells after shRenilla knock-down and 2 samples consisting of sorted CD4+ T cells after shRenilla knock-down.
Contributor(s) Ng C, Aichinger M, Nguyen T, Au C, Najar T, Wu L, Mesa KR, Liao W, Quivy J, Hubert B, Almouzni G, Zuber J, Littman DR
Citation(s) 30975723
Submission date Feb 12, 2019
Last update date May 15, 2019
Contact name Dan Littman
Phone 212-263-7520
Organization name NYU School of Medicine
Street address 430 E 29th St Acls-West Tower 4th Fl Room 460E
City new york
State/province NY
ZIP/Postal code 10016
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (6)
GSM3602263 sgDnmt3a_e19_rep1_ATACseq
GSM3602264 sgDnmt3a_e19_rep2_ATACseq
GSM3602265 sgOlfr2_e2_CD4rep1_ATACseq
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
BioProject PRJNA521992
SRA SRP185732

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
GSE126471_RAW.tar 691.0 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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