GEO series

The HUSH-SETDB1-MORC2 epigenetic repressor complex restricts herpesvirus infection in association with PML nuclear bodies

GSE263436 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 14 samples Submitted 2024/09/24 Platform GPL18573

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 14 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 14 samples: 14 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomesProceedings of the National Academy of Sciences of the United States of America · 2024

Summary (written by the submitters)

The establishment of latent herpes simplex virus 1 (HSV-1) infection is controlled by promyelocytic leukemia nuclear bodies (PML NBs). Viral genomes are recruited to PML NBs structures and chromatinized by repressive H3.3K9me3 modified H3.3 histone variant to form viral DNA-containing PML-NBs (vDCP NBs). Exactly how this occurs is unclear.

Read the full summary ↓

Here we identify an essential role for the HUSH complex and its SETDB1 and MORC2 effectors in the establishment and maintenance of latent herpes simplex virus 1 (HSV-1) infection. ChIP-seq analyses conducted on latently/quiescently infected primary human fibroblasts highlight the association of the H3K9me3 mark with the entire viral genome. We demonstrate the necessity of HUSH, SETDB1, and MORC2 in the establishment of repressive heterochromatin in vDCP NBs. Depletion of these components prior to viral infection results in reduced H3K9me3 levels across the entirety of latent/quiescent HSV-1 genomes, with minimal impact on the cellular genome as a whole. Once latency is established, depletion of HUSH, SETDB1, or MORC2 by shRNAs or the HIV-2ROD Vpx protein, induces the reactivation of HSV-1 in infected primary human fibroblasts as well as in human induced pluripotent stem cell-derived sensory neurons (hiPSDN). We discovered that the viral protein ICP0 induces MORC2 degradation via the proteasome machinery. This process is concurrent with ICP0 capability to initiate full HSV-1 reactivation, as well as the significant reactivation of HSV-1 upon MORC2 depletion in hiPSDN. Our data demonstrate the potent antiviral restriction activity of the HUSH/SETDB1/MORC2 complex to a non-integrated human herpesvirus, its close association with PML NBs, and introduces a new target for anti-herpesvirus therapy.

Published in

The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes

Roubille S, Escure T, Juillard F et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 39589886 · doi:10.1073/pnas.2412258121

This dataset

Open GSE263436 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE263436_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1097546 and SRA study SRP500394. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39589886) ↗

Study design

14 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 14 sample titles: 14 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8191932 BJ, Input, shCtl, Non infected
GSM8191933 BJ, Input, shCtl, Infected with HSV-1 in1374
GSM8191934 BJ, Input, shTASOR, Infected with HSV-1 in1374
GSM8191935 BJ, Input, shMPP8, Infected with HSV-1 in1374
GSM8191936 BJ, Input, shPPHLN1, Infected with HSV-1 in1374
GSM8191937 BJ, Input, shMORC2, Infected with HSV-1 in1374
GSM8191938 BJ, Input, shSETDB1, Infected with HSV-1 in1374
GSM8191939 BJ, ChIP H3K9me3, shCtl, Non infected
GSM8191940 BJ, ChIP H3K9me3, shCtl, Infected with HSV-1 in1374
GSM8191941 BJ, ChIP H3K9me3, shTASOR, Infected with HSV-1 in1374
GSM8191942 BJ, ChIP H3K9me3, shMPP8, Infected with HSV-1 in1374
GSM8191943 BJ, ChIP H3K9me3, shPPHLN1, Infected with HSV-1 in1374
GSM8191944 BJ, ChIP H3K9me3, shMORC2, Infected with HSV-1 in1374
GSM8191945 BJ, ChIP H3K9me3, shSETDB1, Infected with HSV-1 in1374

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