The post-translational modification of heterochromatin factors by the small ubiquitin-like protein SUMO has been implicated at several steps in the establishment and maintenance of transcriptional gene silencing and has been linked to silencing mediated by the Piwi Argonaute (reviewed in Ninova et al., 2019). In animals, NuRD complexes function broadly in developmental gene regulation and transposon silencing ( Ecco et al., 2017 Feschotte and Gilbert, 2012 Ho and Crabtree, 2010). NuRD complexes play a key role in converting chromatin from an active to a silent state, and can be recruited to targets through sequence-independent interactions (e.g., modified chromatin or methylated DNA) or through sequence-specific interactions via the Krüppel-type C2H2 zinc finger protein and other DNA-binding factors ( Ecco et al., 2017 Lupo et al., 2013).

SHREC therefore resembles the nucleosome remodeling and deacetylase (NuRD) complex in animals ( Denslow and Wade, 2007 Torchy et al., 2015). SHREC contains a homolog of type 1 histone deacetylase (HDAC), a homolog of Mi-2 and CHD3 ATP-dependent chromatin remodelers, and a Krüppel-type C2H2 zinc finger protein. In yeast, 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). 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). The Chp1 protein binds H3K9me3 through its conserved chromodomain ( Partridge et al., 2000 Partridge et al., 2002) and is thought to anchor Ago1 within heterochromatin, where it is poised to engage nascent RNA transcripts ( Holoch and Moazed, 2015).

Connections between Argonautes and chromatin are best understood from studies in fission yeast Schizosaccharomyces pombe, where the Argonaute, Ago1, a novel protein, Tas3, and a heterochromatin protein 1 (HP1) homolog, Chp1, comprise an RNA-induced transcriptional silencing (RITS) complex that maintains and expands heterochromatin ( Verdel et al., 2004).

Argonaute-dependent small RNA pathways are linked to chromatin-mediated gene regulation in diverse eukaryotes, including plants, protozoans, fungi, and animals (reviewed in Martienssen and Moazed, 2015). 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).

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