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. Author manuscript; available in PMC: 2022 Sep 1.
Published in final edited form as: Mol Cell. 2022 Mar 28;82(9):1691–1707.e8. doi: 10.1016/j.molcel.2022.03.004

Figure 6. Model.

Figure 6.

(A) The HUSH and NEXT complexes function to control expression of TE transcripts at either the transcriptional or post-transcriptional level, respectively. HUSH is recruited to TE loci decorated with H3K9me3 histone marks and is required for maintaining H3K9me3 levels and transcriptional (txn) suppression. NEXT is recruited to HUSH-bound loci through a physical connection that requires ZCCHC8 and MPP8.

(B) In the absence of NEXT, HUSH can still bind to chromatin, regulate H3K9me3, and maintain low transcription levels. Without NEXT-mediated RNA decay, short pA− transcripts from TE loci are stabilized.

(C) In the absence of HUSH, H3K9me3 levels are not maintained and NEXT is no longer recruited to HUSH-bound loci. TE loci lose transcriptional repression and show an increase in full-length pA+ TE RNAs that, in the case of L1 LINEs, can be export competent and subsequently translated.