Functional Landscape of PCGF Proteins Reveals Both RING1A/B-Dependent-and RING1A/B-Independent-Specific Activities.

Andrea Scelfo,Monica Soldi,Marika Zanotti,Daniel Fernández-Pérez,Simone Tamburri,Elisa Lavarone,Diego Pasini,Tiziana Bonaldi,Karin Johanna Ferrari

doi:10.1016/j.molcel.2019.04.002

Andrea Scelfo, Monica Soldi + Show 7 more

Open Access

https://doi.org/10.1016/j.molcel.2019.04.002

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Abstract

SummaryPolycomb 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.

Highlights

The precise control of specific active and repressed transcriptional states is at the basis of first establishing and maintaining cellular identity (Bracken and Helin, 2009; Orkin and Hochedlinger, 2011)
PRC1, which deposits H2Aub1 through the E3 ligases RING1A/B, forms six biochemically distinct subcomplexes depending on the assembled PCGF protein (PCGF1–PCGF6); it is yet unclear whether these subcomplexes have specific activities
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

Summary

Introduction

The precise control of specific active and repressed transcriptional states is at the basis of first establishing and maintaining cellular identity (Bracken and Helin, 2009; Orkin and Hochedlinger, 2011). The Polycomb group (PcG) protein family provides the major repressive mechanism for defining facultative heterochromatin (Bernstein et al, 2006), an essential step for both embryogenesis and homeostatic development of adult tissues (Aloia et al, 2013; Avgustinova and Benitah, 2016). Polycomb proteins exert their functions in two large multiprotein repressive complexes, PRC1 and PRC2, which are defined by specific core activities that modify histone proteins. Up to four major activities for PRC1 could exist and be active in the same cells, in close relationship with PRC2, but with potentially distinct functions (Pasini and Di Croce, 2016)

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