Molecular Cell
Volume 74, Issue 5, 6 June 2019, Pages 1037-1052.e7
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Article
Functional Landscape of PCGF Proteins Reveals Both RING1A/B-Dependent-and RING1A/B-Independent-Specific Activities

https://doi.org/10.1016/j.molcel.2019.04.002Get rights and content
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Highlights

  • PRC1 complexes retain high target specificity with little compensatory functions

  • PCGF2 defines repressive signatures and PCGF3 and PCGF6 transcription active states

  • RING1A/B is dispensable for the assembly and recruitment of PCGF3 and PCGF6 complexes

  • PCGF3 and PCGF6 complexes bind target genes through specific DNA binding activities

Summary

Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) control cell identity by establishing facultative heterochromatin repressive domains at common sets of target genes. PRC1, which deposits H2Aub1 through the E3 ligases RING1A/B, forms six biochemically distinct subcomplexes depending on the assembled PCGF protein (PCGF1–PCGF6); however, it is yet unclear whether these subcomplexes have also specific activities. Here we show that PCGF1 and PCGF2 largely compensate for each other, while other PCGF proteins have high levels of specificity for distinct target genes. PCGF2 associates with transcription repression, whereas PCGF3 and PCGF6 associate with actively transcribed genes. Notably, PCGF3 and PCGF6 complexes can assemble and be recruited to several active sites independently of RING1A/B activity (therefore, of PRC1). For chromatin recruitment, the PCGF6 complex requires the combinatorial activities of its MGA-MAX and E2F6-DP1 subunits, while PCGF3 requires an interaction with the USF1 DNA binding transcription factor.

Keywords

Polycomb
PCGF
PRC1
USF1
H2A ubiquitination
RING1B
MGA
EZH2
MYC
H3K27me3

Cited by (0)

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These authors contributed equally

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These authors contributed equally

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Present address: Institut Curie, PSL Research University, UMR 144, 26 rue d’Ulm, F-75005 Paris, France

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Lead Contact