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Series GSE181113 Query DataSets for GSE181113
Status Public on Sep 30, 2021
Title Genome surveillance through repression of intronless mobile elements by the HUSH complex
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary All life forms defend their genome against DNA invasion. Eukaryotic cells recognize incoming DNA and limit transcription through repressive chromatin modifications. The human silencing hub (HUSH) complex transcriptionally represses long interspersed element-1 retrotransposons (L1s) and retroviruses through histone H3 Lys9 trimethylation (H3K9me3). How HUSH recognizes and initiates silencing of these invading genetic elements is unknown. Here, we show that HUSH is able to recognize and transcriptionally repress a broad range of long, intronless transgenes. Intron insertion into HUSH-repressed transgenes counteracts repression, even in the absence of intron splicing. HUSH binds transcripts from the target locus, prior to and independent of H3K9me3 deposition, and target transcription is essential for both initiation and propagation of HUSH-mediated H3K9me3. Genomic data reveals how HUSH binds and represses a subset of endogenous intronless genes generated through retrotransposition of cellular mRNAs. Therefore, intronless cDNA, a hallmark of reverse transcription, provides a versatile means to distinguish invading retroelements from host genes and allows HUSH to protect the genome from ‘non-self’ DNA, despite no prior exposure to the invading element. Our findings reveal the existence of a genome surveillance system and explain how it provides immediate protection against newly acquired elements while avoiding inappropriate repression of host genes.
Overall design UV-crosslinked RNA immunoprecipitation followed by next generation sequencing (UV-RIPseq) to identify RNA interactome of Periphilin. ChIPseq to identify methylation changes over lentiviral reporter and CRISPR/Cas9-modified endogenous locus.
Contributor(s) Seczynska M, Bloor S, Martinez Cuesta S, Lehner P
Citation(s) 34794168
Submission date Jul 29, 2021
Last update date Jan 02, 2022
Contact name Sergio Martínez Cuesta
Organization name AstraZeneca
Department Data Sciences and Quantitative Biology, Discovery Sciences
Street address 1 Francis Crick Avenue
City Cambridge
ZIP/Postal code CB2 0AA
Country United Kingdom
Platforms (2)
GPL22790 Illumina MiniSeq (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (26)
GSM5484690 SETDB1KO_Periphilin rep 1
GSM5484691 SETDB1KO_Periphilin rep 2
GSM5484692 SETDB1KO_empty rep 1
BioProject PRJNA750731
SRA SRP330450

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Supplementary file Size Download File type/resource 346.3 Mb (ftp)(http) BW
GSE181113_HA.SKOHA.v2.bed.gz 103.1 Kb (ftp)(http) BED
GSE181113_RAW.tar 6.4 Gb (http)(custom) TAR (of BW) 233.7 Mb (ftp)(http) BW
GSE181113_WTHA.v2.bed.gz 312.1 Kb (ftp)(http) BED 143.2 Mb (ftp)(http) BW 182.1 Mb (ftp)(http) BW
GSE181113_ripseq_genes.txt.gz 6.0 Mb (ftp)(http) TXT
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Processed data are available on Series record
Processed data provided as supplementary file
Raw data are available in SRA

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