Abstract
Heterochromatin protein 1 (HP1) proteins are key factors of eukaryotic heterochromatin that coordinate chromatin compaction and transcriptional gene silencing. Through their multivalency they act as adaptors between histone H3 Lys9 di/trimethyl marks in chromatin and effector complexes that bind to the HP1 chromoshadow domain. Most organisms encode for multiple HP1 isoforms and the molecular mechanisms that underpin their diverse functions in genome regulation remain poorly understood. In fission yeast, the two HP1 proteins Chp2 and Swi6 assume distinct roles and Chp2 is tightly associated with the nucleosome remodeling and deacetylation complex SHREC. Here we show that Chp2 directly engages the SHREC nucleosome remodeler subunit Mit1. The crystal structure of the interaction interface reveals an extraordinarily extensive and specific interaction between the chromoshadow domain of Chp2 and the N terminus of Mit1. The integrity of this interface is critical for high affinity binding and for heterochromatin formation. Comparison with Swi6 shows that the Chp2-Mit1 interface is highly selective and thereby provides the molecular basis for the functional specialization of an HP1 isoform.
Highlights
Eukaryotic genomes are highly organized and division into euchromatic and heterochromatic compartments is crucial for the correct execution of gene expression programs, for establishment of chromosomal structures such as telomeres and centromeres and for protection of the genome from parasitic genetic elements (Grewal and Jia 2007; Schalch 2017)
Small RNAs are produced from pericentromeric heterochromatin loci and guide the RNA interference (RNAi)-induced transcriptional gene silencing complex (RITS) to nascent transcripts, which are subsequently degraded by the RNAi machinery (Volpe et al 2002; Verdel et al 2004; Shimada et al 2016)
In contrast to Swi6, which binds a wide range of client proteins, Chp2 is predominantly associated with the Snf2/HDAC repressor complex (SHREC) that belongs to the family of nucleosome remodeling and deacetylation complexes (NuRDs)
Summary
Eukaryotic genomes are highly organized and division into euchromatic and heterochromatic compartments is crucial for the correct execution of gene expression programs, for establishment of chromosomal structures such as telomeres and centromeres and for protection of the genome from parasitic genetic elements (Grewal and Jia 2007; Schalch 2017). RITS recruits the H3K9 methyltransferase Clr to heterochromatic loci (Zhang et al 2008; Bayne et al 2010), and deposition of the H3K9 methyl marks provides chromatin binding sites for the HP1 proteins Swi and Chp. RITS recruits the H3K9 methyltransferase Clr to heterochromatic loci (Zhang et al 2008; Bayne et al 2010), and deposition of the H3K9 methyl marks provides chromatin binding sites for the HP1 proteins Swi and Chp2 These proteins cannot complement each other’s function in the regulation of transcription at heterochromatic loci (Sadaie et al 2008), and they are found to be part of nonoverlapping complexes (Motamedi et al 2008; Fischer et al 2009). How Chp achieves the specific recruitment of the SHREC complex is not understood
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