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. 2023 Feb 27;42(8):e111717. doi: 10.15252/embj.2022111717

Figure 3. HUSH‐mediated silencing.

Figure 3

The human silencing complex (HUSH) is known to regulate the expression of evolutionary young TEs, such as LINE1 elements, primarily residing within introns. (1) Core subunits of the complex, namely TASOR and PPHLN1, have intrinsic RNA binding capacity which allows them to bind nascent LINE1 transcripts (Castello et al, 2012; Prigozhin et al, 2020). (2) The complex is known to confer transcriptional silencing by recruiting SETDB1:ATF7IP on chromatin, and guiding H3K9me3 deposition at LINE1 loci in an MPP8‐dependent manner (Tchasovnikarova et al, 2015; Timms et al, 2016; Douse et al, 2020). (3) The MPP8 subunit can also recognize H3K9me3 marks through its chromodomain, hence sustaining LINE1 heterochromatinization (Douse et al, 2020). (4) In parallel, both TASOR and MPP8 subunits directly interact with MTR4 and ZCCHC8 components of the Nuclear Exosome Targeting Complex (NEXT). (5) This allows for the recruitment of NEXT at TE loci allowing for targeted RNA decay (Garland et al, 2022).