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DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex

ABSTRACT: DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex

PROVIDER: PRJNA1011851 | ENA |

REPOSITORIES: ENA

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DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex

Project description: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.

2024-03-26 | GSE242143 | GEO

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [CUT&RUN]

2024-03-26 | GSE240384 | GEO

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [Bulk RNA-seq]

2024-03-26 | GSE240386 | GEO

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT cDNA sequencing]

2024-03-26 | GSE262483 | GEO

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT whole genome DNA]

2024-03-26 | GSE262482 | GEO

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [CUT&RUN]

Project description:DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [CUT&RUN]

| PRJNA1003476 | ENA

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [Bulk RNA-seq]

Project description:DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [Bulk RNA-seq]

| PRJNA1003480 | ENA

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT cDNA sequencing]

Project description:DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT cDNA sequencing]

| PRJNA1091962 | ENA

DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT whole genome DNA]

Project description:DNA methylation status determines the sensitivity of repeats to restriction by the HUSH-MORC2 complex [ONT whole genome DNA]

| PRJNA1092053 | ENA

Assessing the impact of the R252W Charcot-Marie-Tooth disease mutation in MORC2 on HUSH-mediated repression

Project description:HeLa cells lacking MORC2 generated through CRISPR/Cas9-mediated gene disruption were reconstituted with either wild-type or R252W mutant MORC2, and re-repression of HUSH target genes assessed by RNA-seq

2017-05-29 | GSE95455 | GEO

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