Fig. 1. HUSH activities and domain structures resemble the RITS complex.

a Genome browser snapshots of TASOR binding and regulation of H3K9me3. Shown are CUT&RUN H3K9me3 tracks in TASOR-positive and TASOR-negative HeLa cells (green); CUT&Tag and ChIP TASOR tracks in TASOR-positive (purple) and TASOR-negative cells; and an IgG control for each technique from control cells (gray). b Heatmaps of the signal from indicated experiments and replicates across 393 TASOR-regulated loci (rows). The sequencing depth of CUT&Tag TASOR experiments was ~4M reads, compared with ~55M reads for ChIP-seq. c Overlaps of 393 TASOR-regulated H3K9me3 peaks with different repeat classes. Since these peaks extend over several kilobases (mean length 6369 bp), several covered more than one annotated repeat. d Coding genes overlapping with TASOR-regulated H3K9me3 peaks were plotted (red dots) on a scatterplot showing gene transcript levels. Raw data were processed from triplicate RNA-seq data on wild-type HeLa cells, mapped to hg38 (ref. ¹⁴). RPKM, reads per kilobase per million mapped reads. e TASOR BioID hits. HUSH subunits are marked in bold. Control refers to TASOR knockout cells treated with biotin but not expressing BirA-tagged TASOR. f Predicted domain architecture of Homo sapiens HUSH subunits, showing similarity with Schizosaccharomyces pombe Chp1 and Tas3. DUF, domain of unknown function. SPOC, Spen ortholog C-terminal. PIN, PilT N-terminus. CD, chromodomain. HUSH, human silencing hub. RITS, RNA-induced transcriptional silencing complex. g Schematic model of HUSH repression.