Polycomb epigenetic silencing is mediated by specific DNA-binding recruiters

Polycomb group (PcG) proteins are essential for regulation of cell identity and development in plants and animals. PcG proteins are organized into diverse Polycomb repressive complexes (PRCs), among which PRC2 is probably the best described and most evolutionarily con­served. The catalytic subunit of PRC2 is able to add three methyl groups to lysine 27 of his­tone H3 (H3K27me3) –– which modifies chromatin structure and, as a result, represses gene expression. The H3K27me3 mark deco­rates thousands of genes in different cell types at distinct developmental stages in plants and animals. The genome-wide distribu­tion of this mark shows that PRC2 activity is targeted to euchromatic genes that are dynamically regulated.

Although the composition and activity of PRC2 is well known, specificity of its tar­geting and regulation is complicated and less clear. PRC2 subunits, as well as the mechanisms for the recruitment of this complex to specific targets, were first identified in the fruit fly, Drosophila melanogaster. In the fly, PRC2 chromatin binding occurs through interactions with Polycomb repres­sive elements (PREs) –– DNA stretches of vari­able length formed by an array of short motifs, which can be located far from target genes and depend on formation of DNA loops to reg­ulate them. The presence and dis­tribution of these motifs within PREs seem to depend on the target gene. The existence of mammalian PREs is more ambiguous, and their definition and the com­ponents that integrate them are more contro­versial. Current models in mammals indicate a complex interplay between cis elements (motifs close to the target gene), DNA-binding factors, CpG islands (cytosine base, followed by a guanine base, in the DNA), and noncoding RNAs in PRC2 recruitment.

There are also open questions on how PRC2 proteins are anchored to chromatin (everything making up chromosomes) in plants. In the attached article and editorial, authors have now confirmed the genetic general action of tandem PRE–transcription factor complexes in anchoring PRC2 to spe­cific loci in the tiny mustand plant, Arabidopsis thaliana, indicating evolution­ary conservation of the mechanisms between insects and plants.

Authors identified transcription factor families that bind to these PREs, co-localize with PRC2 on chromatin, physically interact with and recruit PRC2, and are required for PRC2-mediated gene silencing. Two of the cis sequence motifs enriched in the PREs are cognate binding sites for the identified transcription factors and are necessary and sufficient for PRE activity. These intriguing findings indicate that PRC2 recruitment in the plant Arabidopsis relies, in large part, on binding of trans-acting factors (motifs distant from the target gene), to cis-localized DNA sequence motifs.

Nature Genetics Oct 2o17; 49: 1546–1552 [article] and pp 1416–1417 [editorial]

This entry was posted in Center for Environmental Genetics. Bookmark the permalink.