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Series GSE240386 Query DataSets for GSE240386
Status Public on Mar 26, 2024
Title DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [Bulk RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The human silencing hub (HUSH) complex binds to transcripts of LINE-1 retrotransposons (L1s) and other genomic repeats, recruiting MORC2 and other effectors to remodel chromatin. However, how HUSH and MORC2 operate alongside DNA methylation, a central epigenetic regulator of repeat transcription, remains poorly understood. Here we interrogate this relationship in human neural progenitor cells (hNPCs), a somatic model of brain development that tolerates removal of DNA methyltransferase DNMT1. Upon loss of MORC2 or HUSH subunit TASOR in hNPCs, L1s remain silenced by robust promoter methylation. However, genome demethylation and activation of evolutionarily-young L1s attracts MORC2 binding. Simultaneous depletion of DNMT1 and MORC2 causes massive accumulation of L1 transcripts. We identify the same mechanistic hierarchy at pericentromeric α-satellites and clustered protocadherin genes, repetitive elements important for chromosome structure and neurodevelopment respectively. Our data delineate the independent epigenetic control of repeats in somatic cells, with implications for understanding the vital functions of HUSH-MORC2 in hypomethylated contexts throughout human development.
 
Overall design Expression levels of genes and transposable elements in human neuroepithelial-like stem cells (hNSC) was examined by Bulk-RNA sequencing in five different conditions: LacZ - CRISPRi (a control targetting a bacterial gene which is not present in the human genome), TASOR - CRISPRi, MORC2 - CRISPRi, DNMT1 - CRISPRi and DNMT1&MORC2 - CRISPRi.
 
Contributor(s) Pandiloski N
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Submission date Aug 08, 2023
Last update date Mar 27, 2024
Contact name Ninoslav Pandiloski
E-mail(s) ninoslav.pandiloski@med.lu.se
Organization name Lund University
Street address Sölvegatan 17
City Lund
ZIP/Postal code 223 62
Country Sweden
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (27)
GSM7697290 MORC2_and_TASOR_CRISPRi_control_rep1
GSM7697291 MORC2_and_TASOR_CRISPRi_control_rep2
GSM7697292 MORC2_and_TASOR_CRISPRi_control_rep3
This SubSeries is part of SuperSeries:
GSE242143 DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex
Relations
BioProject PRJNA1003480

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
GSE240386_RAW.tar 767.7 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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