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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
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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.
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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.
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Contributor(s) |
Pandiloski N |
Citation missing |
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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
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Organization name |
Lund University
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Street address |
Sölvegatan 17
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City |
Lund |
ZIP/Postal code |
223 62 |
Country |
Sweden |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (27)
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This SubSeries is part of SuperSeries: |
GSE242143 |
DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex |
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Relations |
BioProject |
PRJNA1003480 |