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

ABSTRACT: The Human Silencing Hub (HuSH) complex is a complex that silences retrotransposable elements invertebrates. Here, we identify a second HuSH complex, designated HuSH2, which is centered aroundTASOR2, a paralog of the core TASOR protein in HuSH. Our findings reveal that HuSH and HuSH2 localize todistinct and non-overlapping genomic loci. Specifically, HuSH localizes to and represses LINE-1retrotransposons, whereas HuSH2 targets and represses KRAB-ZNFs and interferon signaling and responsegenes. 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 andother 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 tuneHuSH-mediated silencing. This study offers insights into the interplay of HuSH complexes, highlighting theirvital role in retrotransposon regulation.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Zena Jensvold

LAB HEAD: Peter W

PROVIDER: PXD049085 | Pride | 2024-09-24

REPOSITORIES: Pride

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			Action	DRS
	200803_IP-MPP8_Lewis.raw	Raw
	200803_IP-ctrl-293F_Lewis.raw	Raw
	200803_IP_PPHLN-1_Lewis.raw	Raw
	200803_IP_TASOR_Lewis.raw	Raw
	293F_Ctrl_Lewis_20200529.raw	Raw

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