Variant Polycomb complexes in Drosophila consistent with ancient functional diversity

Abstract

Polycomb group (PcG) mutants were first identified in Drosophila on the basis of their failure to maintain proper Hox gene repression during development. The proteins encoded by the corresponding fly genes mainly assemble into one of two discrete Polycomb repressive complexes: PRC1 or PRC2. However, biochemical analyses in mammals have revealed alternative forms of PRC2 and multiple distinct types of noncanonical or variant PRC1. Through a series of proteomic analyses, we identify analogous PRC2 and variant PRC1 complexes in Drosophila , as well as a broader repertoire of interactions implicated in early development. Our data provide strong support for the ancient diversity of PcG complexes and a framework for future analysis in a longstanding and versatile genetic system.

Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1

“…The binding of CBX subunits of cPRC1 to H3K27me3, and the recognition of H2AK119ub1 by PRC2.2-associated factors JARID2 or AEBP2, has inspired multiple hierarchical or interdependent recruitment models (Baile et al 2022;Kang et al 2022;Kim and Kingston 2022;Piunti and Shilatifard 2021;Schuettengruber et al 2017;Loubiere et al 2019;Blackledge et al 2020;Tamburri et al 2020). However, in spite of cooperative cross-talk, in vivo studies showed that there is no crucial dependency between PRC1 and PRC2 that is essential for repression of canonical Polycomb targets (Bonnet et al 2022;Cohen et al 2021;Leeb et al 2010;Pengelly et al 2015;Sijm et al 2022;Zepeda-Martinez et al 2020).…”

“…Both PRC1 and PRC2 form subcomplexes through the incorporation of accessory subunits or through the combinatorial assembly of paralogous components (Baile et al 2022;Kang et al 2022;Piunti and Shilatifard 2021;Kim and Kingston 2022). ncPRC1 and cPRC1 are distinguished by the mutually exclusive binding of either CBX (cPRC1) or RYBP (ncPRC1) (Gao et al 2012).…”

“…PcG proteins function as part of two main classes of multi-protein complexes, named Polycomb Repressive Complex (PRC) 1 and 2, which change chromatin structure across multiple scales (Baile et al 2022;Kang et al 2022;Kim and Kingston 2022;Piunti and Shilatifard 2021;Schuettengruber et al 2017;Loubiere et al 2019). The PRC2 methyltransferases mediate mono-, di-and tri-methylation of H3K27 (H3K27me3), whereas the PRC1s mediate chromatin compaction and mono-ubiquitylation of H2A (H2Aub1) on Lys 118, 119 or 120 in Drosophila, mammals or Arabidopsis, respectively (Fig.…”

“…The PRC1 class can be subdivided in canonical (cPRC1) and non-canonical PRC1 (ncPRC1) (Baile et al 2022;Kang et al 2022;Loubiere et al 2019;Piunti and Shilatifard 2021).…”

Polycomb protein binding and looping in the ON transcriptional state

“…The PcG genes encode a group of highly conserved proteins required for maintenance of the silenced state of important developmental genes (3)(4)(5). There are two main Polycomb-repressive complexes (PRCs) in both Drosophila and mammals, named PRC1 and PRC2, with both canonical and variant forms (6,7). PRC2 contains the histone methyltransferase E(z) in Drosophila (or EZH1/2 in mammals) that trimethylates histone H3 lysine 27 (H3K27me3), which covers repressed canonical PcG target genes.…”