Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop.

ABSTRACT: Epigenetic inheritance of transcriptional silencing is traditionally attributed to chromatin-based mechanisms in which Argonaute-small RNA complexes recruit histone-modifying enzymes. Here we show that, in Caenorhabditis elegans, the nuclear Argonaute HRDE-1 maintains germline transcriptional repression independently of canonical heterochromatin marks. Using inducible, germline-specific HRDE-1 depletion combined with nuclear sorting, CUT&Tag, and nascent transcription profiling, we identified endogenous genes that become transcriptionally activated upon loss of HRDE-1 despite retaining H3K9me3 and H3K23me3. HRDE-1 directly restrains RNA polymerase II (Pol II) while simultaneously promoting polyUG-dependent amplification of antisense 22G-RNAs in perinuclear condensates, thereby coupl

SUBMITTER: Rojas AML 

PROVIDER: S-EPMC12687788 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature