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Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing [RNA-seq]

GSE234280 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/09/23 Platform GPL24676
Summary
The Human Silencing Hub (HuSH) complex is a complex that silences retrotransposable elements in vertebrates. Here, we identify a second HuSH complex, designated HuSH2, which is centered around TASOR2, a paralog of the core TASOR protein in HuSH. Our findings reveal that HuSH and HuSH2 localize to distinct and non-overlapping genomic loci. Specifically, HuSH localizes to and represses LINE-1 retrotransposons, whereas HuSH2 targets and represses KRAB-ZNFs and interferon signaling and response genes. We use in silico protein structure predictions to simulate MPP8 interactions with TASOR paralogs, guiding amino acid substitutions that disrupted binding to HuSH complexes. These MPP8 transgenes and other constructs reveal the importance of HuSH complex quantities in regulating LINE-1 activity. Furthermore, our results suggest that dynamic changes in TASOR and TASOR2 expression enable cells to finely tune HuSH-mediated silencing. This study offers insights into the interplay of HuSH complexes, highlighting their vital role in retrotransposon regulation.
Published in
Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing
Jensvold ZD, Flood JR, Christenson AE et al. · Nature communications 2024 · PMID 39489739 · doi:10.1038/s41467-024-53761-w
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Also filed as BioProject PRJNA980681 and SRA study SRP441353. Searching any of these in the dataset finder brings you back here.

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