Abstract
The polycomb group (PcG) proteins are a large and diverse family that epigenetically repress the transcription of key developmental genes. They form three broad groups of polycomb repressive complexes (PRCs) known as PRC1, PRC2 and Polycomb Repressive DeUBiquitinase, each of which modifies and/or remodels chromatin by distinct mechanisms that are tuned by having variable compositions of core and accessory subunits. Until recently, relatively little was known about how the various PcG proteins assemble to form the PRCs; however, studies by several groups have now allowed us to start piecing together the PcG puzzle. Here, we discuss some highlights of recent PcG structures and the insights they have given us into how these complexes regulate transcription through chromatin.
Highlights
The development of a multicellular eukaryotic organism is a highly complex process that requires exact control of specific transcriptional programs in a spatially and temporally regulated manner
polycomb group (PcG) functional diversity derives from structural diversity and our current understanding suggests that the PcG proteins form three distinct groups of enzymatic complexes, each with the ability to carry out a specific epigenetic modification (Figure 1) [9,10]: polycomb repressive complex 1 (PRC1) complexes are E3 ubiquitin ligases that monoubiquitinate lysine 119 of histone H2A (H2AK119ub1) and perform ubiquitination-independent chromatin compaction, and possibly interact directly with the transcription machinery; Polycomb Repressive DeUBiquitinase (PR-DUB) opposes the action of PRC1 by deubiquitinating H2AK119; polycomb repressive complex 2 (PRC2) complexes are methyltransferases that target histone H3 lysine 27 for mono, di- and trimethylation (H3K27me1, 2, 3)
Some insights into the mechanism and targeting of PRC1 E3 ligase activity toward H2AK119 have been provided by a recent crystal structure of the RING1B/PCGF4 Ring domain heterodimer fused to the E2 ligase UbcH5c bound to a nucleosome (Figure 2E) [11]
Summary
The development of a multicellular eukaryotic organism is a highly complex process that requires exact control of specific transcriptional programs in a spatially and temporally regulated manner. PcG functional diversity derives from structural diversity and our current understanding suggests that the PcG proteins form three distinct groups of enzymatic complexes, each with the ability to carry out a specific epigenetic modification (Figure 1) [9,10]: polycomb repressive complex 1 (PRC1) complexes are E3 ubiquitin ligases that monoubiquitinate lysine 119 of histone H2A (H2AK119ub1) and perform ubiquitination-independent chromatin compaction, and possibly interact directly with the transcription machinery; Polycomb Repressive DeUBiquitinase (PR-DUB) opposes the action of PRC1 by deubiquitinating H2AK119; polycomb repressive complex 2 (PRC2) complexes are methyltransferases that target histone H3 lysine 27 for mono-, di- and trimethylation (H3K27me1, 2, 3).
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