Abstract
Eukaryotic cells use guided search to coordinately control dispersed genetic elements. Argonaute proteins and their small RNA cofactors engage nascent RNAs and chromatin-associated proteins to direct transcriptional silencing. The small ubiquitin-like modifier (SUMO) has been shown to promote the formation and maintenance of silent chromatin (called heterochromatin) in yeast, plants, and animals. Here, we show that Argonaute-directed transcriptional silencing in Caenorhabditis elegans requires SUMOylation of the type 1 histone deacetylase HDA-1. Our findings suggest how SUMOylation promotes the association of HDAC1 with chromatin remodeling factors and with a nuclear Argonaute to initiate de novo heterochromatin silencing.
Highlights
Argonautes are an ancient family of proteins that utilize short nucleic acid guides to find and regulate cognate RNAs
The small ubiquitin-like modifier (SUMO) and histone deacetylase (HDAC) pathways promote piRNA silencing In C. elegans, silencing initiated by the Piwi Argonaute PRG-1 depends on chromatin modifications at the target locus and on a group of worm-specific Argonautes (WAGOs), including nuclear-localized family members WAGO-9/HRDE-1 and WAGO-10 (Ashe et al, 2012; Bagijn et al, 2012; Lee et al, 2012; Shirayama et al, 2012) and nuage-localized family members WAGO-1 and WAGO-4 (Gu et al, 2009; Shirayama et al, 2012; Xu et al, 2018)
When we introduced the piRNA sensor into the HDA-1 SUMO-acceptor site mutants, we found that whereas the piRNA sensor remained silent in the single-site mutants (n = 30), it was expressed in 100% of HDA-1(KKRR) worms (Figure 2C)
Summary
Argonautes are an ancient family of proteins that utilize short nucleic acid guides (usually composed of 20–30 nts of RNA) to find and regulate cognate RNAs (reviewed in Meister, 2013). The Chp protein binds H3K9me through its conserved chromodomain (Partridge et al, 2000; Partridge et al, 2002) and is thought to anchor Ago within heterochromatin, where it is poised to engage nascent RNA transcripts (Holoch and Moazed, 2015). Low-level transcription of heterochromatin is thought to create a platform for propagating small-RNA amplification and heterochromatin maintenance (reviewed in Holoch and Moazed, 2015). A protein complex termed SHREC (Snf2/Hdac-containing Repressor complex) has been linked to both the establishment and maintenance of heterochromatin and transcriptional silencing (Job et al, 2016; Motamedi et al, 2008; Sugiyama et al, 2007). SHREC contains a homolog of type 1 histone deacetylase (HDAC), a homolog of Mi-2 and CHD3 ATP-dependent chromatin remodelers, and a Kruppel-type C2H2 zinc finger protein.
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