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Series GSE77779 Query DataSets for GSE77779
Status Public on May 08, 2016
Title Protracted NP95 binding to hemimethylated DNA disrupts SETDB1-mediated proviral silencing [ChIP-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genetic ablation of the maintenance methyltransferase Dnmt1 induces widespread demethylation and transcriptional activation of CpG-rich IAP (intracisternal A particle) proviruses. Here, we report that this phenomenon is not simply a consequence of loss of DNA methylation. By exploiting conditional deletions of Dnmt1 and Np95, each of which is essential for maintenance methylation, we find that while IAPs are indeed de-repressed in Dnmt1-ablated embryos and embryonic stem cells (ESCs), these proviruses remain silenced in Np95-ablated cells, despite similar kinetics of passive demethylation. Paradoxically, transient IAP activation in Dnmt1-ablated ESCs requires the presence of NP95. We subsequently show that in the absence of NP95, the H3K9 methyltransferase SETDB1 maintains IAP silencing; while in the absence of DNMT1, prolonged binding of NP95 to hemimethylated DNA perturbs SETDB1-dependent H3K9me3 deposition. Taken together, these observations reveal that following acute loss of Dnmt1, H3K9 methylation-dependent IAP silencing is disrupted by aberrant NP95 binding to hemimethylated DNA.
Overall design RNA-seq for Np95, Dnmt1 and Setdb1 wt, single conditional KO (cKO) and double cKO ES cells; RRBS-seq for Dnmt1 and Np95 single and double cKO ESCs; Myc-tagged NP95, DNMT1 ChIP-seq; and wt and Np95wt and cKO H3K9me3 ChIP-seq.
Contributor(s) Koseki H, Lorincz MC, Sharif J
Citation(s) 27151458
Submission date Feb 10, 2016
Last update date May 15, 2019
Contact name Takaho A. Endo
Organization name RIKEN
Department IMS
Lab Laboratory for Integrative Genomics
Street address 1-7-22 Suehiro, Tsurumi
City Yokohama
State/province Kanagawa
ZIP/Postal code 230-0045
Country Japan
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (9)
GSM2059180 DN+Myc-Np95 cDKO ESC [ChIP-seq]
GSM2059181 DN+Myc-Np95 wt ESC [ChIP-seq]
GSM2059182 Myc-Dnmt1 wt ESC [ChIP-seq]
This SubSeries is part of SuperSeries:
GSE77781 Protracted NP95 binding to hemimethylated DNA disrupts SETDB1-mediated proviral silencing
BioProject PRJNA311544
SRA SRP069862

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Supplementary file Size Download File type/resource
GSE77779_RAW.tar 65.6 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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