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Series GSE159933 Query DataSets for GSE159933
Status Public on Sep 07, 2021
Title Morc3 silences endogenous retroviruses by enabling Daxx-mediated H3.3 incorporation [ChIP-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Endogenous retroviruses (ERVs) comprise a significant portion of mammalian genomes. Although, specific ERV loci feature regulatory roles for host gene expression, most ERV integrations are transcriptionally repressed by Setdb1 mediated H3K9me3 and DNA methylation. However, the protein network which regulates deposition of these chromatin modifications is still incompletely understood. Here, we performed a genome-wide sgRNA screen for genes involved in ERV silencing and identified the GHKL ATPase protein Morc3 as top scoring hit. Morc3 knock-out cells display de-repression, reduced H3K9me3 and increased chromatin accessibility of distinct ERV classes. We found that the GHKL ATPase domain of Morc3 is critical for ERV silencing, since mutants which cannot bind ATP, or which are defective in ATP hydrolysis cannot rescue the Morc3 ko phenotype. Proteomic analysis revealed that Morc3 mutant protein which cannot bind ATP fails to interact with the H3.3 chaperone Daxx. This interaction depends on Morc3 sumoylation, as Daxx lacking the SUMO interaction domain shows reduced association with Morc3. Notably, in Morc3 ko cells, we observed strongly reduced H3.3 on Morc3 binding sites. Thus, our data demonstrate Morc3 as critical regulator of Daxx-mediated H3.3 incorporation into ERV regions.
 
Overall design ChIP analysis of the H3K4me3, H3K9me3 and H3K27ac histone modifications, H3.3 histone variant, Setdb1 and wild type and mutant Morc3 in different mouse embryonic stem cell lines
 
Contributor(s) Groh S, de Almeida GP, Schotta G
Citation(s) 34650047
Submission date Oct 23, 2020
Last update date Nov 03, 2021
Contact name Gunnar Schotta
E-mail(s) gunnar.schotta@bmc.med.lmu.de
Phone 089218075422
Organization name LMU Munich
Department Biomedical Center
Street address Grosshaderner Strasse 9
City Planegg-Martinsried
ZIP/Postal code 82152
Country Germany
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (47)
GSM4850876 ChIP_Input_WT26
GSM4850877 ChIP_FLAG_K9G1
GSM4850878 ChIP_H3K9me3_KO27_2
This SubSeries is part of SuperSeries:
GSE159936 Morc3 silences endogenous retroviruses by enabling Daxx-mediated H3.3 incorporation
Relations
BioProject PRJNA670920
SRA SRP288314

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
GSE159933_RAW.tar 21.2 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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