Mitotic Inheritance of PRC2-Mediated Silencing: Mechanistic Insights and Developmental Perspectives

Abstract

Maintenance of gene repression by Polycomb Repressive Complex 2 (PRC2) that catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) is integral to the orchestration of developmental programs in most multicellular eukaryotes. Faithful inheritance of H3K27me3 patterns across replication ensures the stability of PRC2mediated transcriptional silencing over cell generations, thereby safeguarding cellular identities. In this review, we discuss the molecular and mechanistic principles that underlie H3K27me3 restoration after the passage of the replication fork, considering recent advances in different model systems. In particular, we aim at emphasizing parallels and differences between plants and other organisms, focusing on the recycling of parental histones and the replenishment of H3K27me3 patterns post-replication thanks to the remarkable properties of the PRC2 complex. We then discuss the necessity for fine-tuning this genuine epigenetic memory system so as to allow for cell fate and developmental transitions. We highlight recent insights showing that genome-wide destabilization of the H3K27me3 landscape during chromatin replication participates in achieving this flexible stability and provides a window of opportunity for subtle transcriptional reprogramming.

Polycomb Repression without Bristles: Facultative Heterochromatin and Genome Stability in Fungi

“…DNA replication requires disassembly of nucleosomes and eviction of DNA-and chromatin-interacting proteins. While strand-specific mechanisms of histone recycling have been uncovered (reviewed in [13]), it is not fully understood how H3K27me3 is reestablished following passage of the replication fork. PRC2 writes and reads H3K27me3, and colocalizes at replication forks, where it can aid DNA replication [39][40][41][42], suggesting a model of maintenance wherein PRC2 reestablishes H3K27me3 domains using recycled, H3K27me3-modified histones as a guide [43].…”

“…The Reader may directly or indirectly recruit histone deacetylase (HDAC; 10) complexes, which-in combination with repressive chromatin remodeling factors (CRF R; 11)-aid in Reader release from H3K4me3 (12). Chromatin-binding adaptors bound to core PRC2 re-methylate regions destined to be facultative heterochromatin (13).…”

“…There is no evidence for clear homologs of many PRC1 subunits, including KDM2B and JARID2, in fungal genomes. One catalytic activity of PRC1 is ubiquitination of H2A (H2AK118ub1 in flies, H2AK119ub1 in mammals, and H2AK121ub1 in plants), which is thought to result in transcriptional repression (reviewed in [13,17,48,96]). However, this model has not been investigated in any detail in fungi, simply because true Pc proteins are lacking from both fungi and plants [97,98]; thus, all facultative heterochromatin generated by "polycomb" PRC1 complexes must be generated by different mechanisms.…”

“…Compared to the breadth of information amassed in plants and animals (see recent reviews for summaries, e.g., [11][12][13][14][15][16][17][18][19]), the study of facultative heterochromatin in fungi can still be considered an immature field. Even though this form of heterochromatin had been recognized as important on H3K27me3 levels (Connolly and Freitag, unpublished results).…”

Knowing When to Silence: Roles of Polycomb-Group Proteins in SAM Maintenance, Root Development, and Developmental Phase Transition

“…In Drosophila, PRC2 is composed of four core components, including the SET domain-containing histone methyltransferase enhancer of zeste [E(z)], Suppressor of Zeste 12 [Su(z)12], Extra sex combs (Esc), and Nucleosome remodeling factor 55 kDa subunit (Nurf55) or p55 [8] (Table 1). In Arabidopsis (Arabidopsis thaliana), members of these core subunits are present in multigene families.…”