Facultative heterochromatin is marked by the repressive histone modification H3K27me3 in eukaryotes. Deposited by the PRC2 complex, H3K27me3 is essential for regulating gene expression during development, and chromatin bearing this mark is generally considered transcriptionally inert. The PRC2 complex has also been linked to programmed DNA elimination during development in ciliates such as Paramecium. Due to a lack of mechanistic insight, a direct involvement has been questioned as most eliminated DNA segments in Paramecium are shorter than the size of a nucleosome. Here, we identify two sets of histone methylation readers essential for PRC2-mediated DNA elimination in Paramecium: Firefly1/2 and Mayfly1-4. The chromodomain proteins Firefly1/2 act in tight association with TFIIS4, a transcription elongation factor required for noncoding RNA transcription. These noncoding transcripts act as scaffolds for sequence-specific targeting by PIWI-bound sRNAs, resulting in local nucleosome depletion and DNA elimination. Our findings elucidate the molecular mechanism underlying the role of PRC2 in PIWI-mediated DNA elimination and suggest that its role in IES elimination may be to activate rather than repress transcription.
Keywords: H3K27me3; H3K9me3; Heterochromatin; PRC2; Small RNA.
© 2024. The Author(s).