Abstract
More than 80 years ago, the first Polycomb-related phenotype was identified in Drosophila melanogaster. Later, a group of diverse genes collectively called Polycomb group (PcG) genes were identified based on common mutant phenotypes. PcG proteins, which are well-conserved in animals, were originally characterized as negative regulators of gene transcription during development and subsequently shown to function in various biological processes; their deregulation is associated with diverse phenotypes in development and in disease, especially cancer. PcG proteins function on chromatin and can form two distinct complexes with different enzymatic activities: Polycomb repressive complex 1 (PRC1) is a histone ubiquitin ligase and PRC2 is a histone methyltransferase. Recent studies have revealed the existence of various mutually exclusive PRC1 and PRC2 variants. In this Review, we discuss new concepts concerning the biochemical and molecular functions of these new PcG complex variants, and how their epigenetic activities are involved in mammalian development and cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 326-345 |
| Number of pages | 20 |
| Journal | Nature Reviews Molecular Cell Biology |
| Volume | 22 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2021 |
Funding
The two PCGF proteins present in canonical PRC1 — MEL18 (PCGF2) or its homologue BMI1 (PCGF4) — are involved in maintaining the integrity of the complex36,37. These proteins can be found also in non-canonical PRC1, and there is no indication they have different functions in the different variants. Interestingly, BMI1, but not MEL18, was able to strongly stimulate the catalytic activity of RING1B in ubiquitin ligation assays in vitro38. This observation is supported by studies of Bmi1 null mouse embryonic fibroblasts, which have
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
